Identification

Name
Fostamatinib
Accession Number
DB12010
Type
Small Molecule
Groups
Approved, Investigational
Description

Fostamatinib has been investigated for the treatment and basic science of Rheumatoid Arthritis and Immune Thrombocytopenic Purpura (ITP). It was approved on April 17, 2018 under the trade name Tavalisse for use in ITP [8]. Fostamatinib has also been granted orphan drug status by the FDA [8].

Structure
Thumb
Synonyms
Not Available
External IDs
R-788 FREE ACID / R-935788 FREE ACID / R788 FREE ACID / R935788 FREE ACID
Product Ingredients
IngredientUNIICASInChI Key
Fostamatinib disodium86EEZ49YVB914295-16-2ZQGJCHHKJNSPMS-UHFFFAOYSA-L
Active Moieties
NameKindUNIICASInChI Key
TamatinibprodrugRC3A285J2G841290-80-0NHHQJBCNYHBUSI-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
TavalisseTablet100 mg/1OralRigel Pharmaceuticals, Inc.2018-05-09Not applicableUs
TavalisseTablet150 mg/1OralRigel Pharmaceuticals, Inc.2018-05-09Not applicableUs
Categories
UNII
SQ8A3S5101
CAS number
901119-35-5
Weight
Average: 580.4595
Monoisotopic: 580.148291177
Chemical Formula
C23H26FN6O9P
InChI Key
GKDRMWXFWHEQQT-UHFFFAOYSA-N
InChI
InChI=1S/C23H26FN6O9P/c1-23(2)21(31)30(11-38-40(32,33)34)20-14(39-23)6-7-17(28-20)27-19-13(24)10-25-22(29-19)26-12-8-15(35-3)18(37-5)16(9-12)36-4/h6-10H,11H2,1-5H3,(H2,32,33,34)(H2,25,26,27,28,29)
IUPAC Name
{[6-({5-fluoro-2-[(3,4,5-trimethoxyphenyl)amino]pyrimidin-4-yl}amino)-2,2-dimethyl-3-oxo-2H,3H,4H-pyrido[3,2-b][1,4]oxazin-4-yl]methoxy}phosphonic acid
SMILES
COC1=CC(NC2=NC=C(F)C(NC3=NC4=C(OC(C)(C)C(=O)N4COP(O)(O)=O)C=C3)=N2)=CC(OC)=C1OC

Pharmacology

Indication

Fostamatinib is indicated for use in the treatment of chronic immune thrombocytopenia (ITP) in patients who have had insufficient response to previous therapy [Label].

Associated Conditions
Pharmacodynamics

The active metabolite of fostamatinib, R406, inhibits signal transduction by Fcγ receptors involved in the antibody-mediated destruction of platelets by immune cells in chronic ITP [1, 2]. This results in increased platelet counts in this population.

R406 produces inhibition of T and B lymphocyte activation by T-cell receptors (TCRs) and B-cell receptors (BCRs) respectively [1, 2]. It can also inhibit signalling via Fcε receptors which could have applications in treating allergic symptoms through prevention of mast cell degranulation [2, 3]. Inhibition of Fc receptor signalling system also affected by R406 suppresses both dendritic cell maturation and antigen presentation and may contribute to the effects of fostamatinib [4]. As a knock-on effect of disabling signal transduction from Fc receptors, TCRs, and BCRs, the production of inflammatory mediators and cytokines like tumour necrosis factor α, leukotriene C4, interleukin-8, and granulocyte-macrophage colony-stimulating factor.

Fostamatinib can produce hypertension through off-target effects [5]

Mechanism of action

The active metabolite of fostamatinib, R406, is an inhibitor of spleen tyrosine kinase (Syk) [2]. It binds reversibly to the ATP binding pocket with high affinity (Ki = 30nM), inhibiting the kinase activity with an IC50 of 41nM.

Syk is a cytosolic protein kinase and part of the signalling cascade which occurs with Fc receptors, TCRs, and BCRs [1]. It contains two src homology 2 (SH2) domains separated by a linker domain. These SH2 domains bind to tyrosine residues on the immunoreceptor tyrosine-based activating motif phosphorylated by Lyn, another kinase in the cascade. This motif is located on the cytoplasmic regions of several immune receptors including Fc receptors, TCRs, BCRs, and natural killer cell receptors. The flexibility provided by the linker enables the protein to bind to many receptor types. Inhibition of Syk suppresses downstream signal transduction [2].

While Syk plays a role in some pathways involved in the generation of the oxidative burst by neutrophils or phagocytosis by macrophages, R406 does not have a significant effect on these processes [2]. This is likely due to redundant pathways which do not involve Syk. Similarly Syk does not produce significant effects on platelet activation despite its involvement in glycoprotein IV and integrin based signalling. Activation of antibody-dependent cell-mediated toxicity by natural killer cells is also unaffected despite the involvement of Syk in Fc receptor signalling [1].

R406 binds to the adenosine A3 receptor as an antagonist as well as the adenosine and monoamine uptake transporters as an inhibitor [2, 5]. It has also been found to be an inhibitor of UDP glucuronosyltransferase UGT1A1, phosphodiesterase PDE5, fatty acid amide hydrolase, 5-lipoxygenase, cathepsin L, and cathepsin S [5]. R406 appears to inhibit a wide range of kinases at higher concentrations [5]. It is thought that inhibition of some of these targets may be responsible for the increase in blood pressure seen with fostamatinib.

TargetActionsOrganism
ATyrosine-protein kinase SYK
inhibitor
Human
UAdenosine receptor A3
antagonist
Human
Uvesicular monoamine transporter 2 (VMAT2)
inhibitor
Human
UFatty-acid amide hydrolase 1
inhibitor
Human
UEquilibrative nucleoside transporter 1
inhibitor
Human
UUDP-glucuronosyltransferase 1-1
inhibitor
Human
UcGMP-specific 3',5'-cyclic phosphodiesterase
inhibitor
Human
UArachidonate 5-lipoxygenase
inhibitor
Human
UCathepsin S
inhibitor
Human
UCathepsin L1
inhibitor
Human
UTyrosine-protein kinase ABL1
inhibitor
Human
UCalcium-dependent protein kinase 1
inhibitor
Plasmodium falciparum (isolate 3D7)
USerine/threonine-protein kinase PknB
inhibitor
Mycobacterium tuberculosis
URibosomal protein S6 kinase alpha-6
inhibitor
Human
UNon-receptor tyrosine-protein kinase TYK2
inhibitor
Human
UAtypical kinase COQ8A, mitochondrial
inhibitor
Human
UTyrosine-protein kinase JAK1
inhibitor
Human
UHepatocyte growth factor receptor
inhibitor
Human
USerine/threonine-protein kinase NIM1
inhibitor
Human
USerine/threonine-protein kinase MST4
inhibitor
Human
UcAMP-dependent protein kinase catalytic subunit alpha
inhibitor
Human
USerine/threonine-protein kinase 24
inhibitor
Human
USerine/threonine-protein kinase 3
inhibitor
Human
UTyrosine-protein kinase Tec
inhibitor
Human
USerine/threonine-protein kinase 33
inhibitor
Human
USerine/threonine-protein kinase 35
inhibitor
Human
USerine/threonine-protein kinase 36
inhibitor
Human
USerine/threonine-protein kinase 38
inhibitor
Human
USerine/threonine-protein kinase 38-like
inhibitor
Human
USTE20/SPS1-related proline-alanine-rich protein kinase
inhibitor
Human
USerine/threonine-protein kinase TAO1
inhibitor
Human
USerine/threonine-protein kinase TAO2
inhibitor
Human
USerine/threonine-protein kinase TAO3
inhibitor
Human
USerine/threonine-protein kinase TBK1
inhibitor
Human
UAngiopoietin-1 receptor
inhibitor
Human
UDual specificity testis-specific protein kinase 1
inhibitor
Human
UTGF-beta receptor type-1
inhibitor
Human
UTGF-beta receptor type-2
inhibitor
Human
UTyrosine-protein kinase receptor Tie-1
inhibitor
Human
USerine/threonine-protein kinase tousled-like 1
inhibitor
Human
USerine/threonine-protein kinase tousled-like 2
inhibitor
Human
UTRAF2 and NCK-interacting protein kinase
inhibitor
Human
UNon-receptor tyrosine-protein kinase TNK1
inhibitor
Human
UActivated CDC42 kinase 1
inhibitor
Human
USerine/threonine-protein kinase TNNI3K
inhibitor
Human
UTestis-specific serine/threonine-protein kinase 1
inhibitor
Human
UDual specificity protein kinase TTK
inhibitor
Human
UTyrosine-protein kinase TXK
inhibitor
Human
UTyrosine-protein kinase receptor TYRO3
inhibitor
Human
USerine/threonine-protein kinase ULK1
inhibitor
Human
USerine/threonine-protein kinase ULK2
inhibitor
Human
USerine/threonine-protein kinase ULK3
inhibitor
Human
UWee1-like protein kinase
inhibitor
Human
UTyrosine-protein kinase Yes
inhibitor
Human
UMitogen-activated protein kinase kinase kinase 19
inhibitor
Human
UMitogen-activated protein kinase kinase kinase MLT
inhibitor
Human
UTyrosine-protein kinase ZAP-70
inhibitor
Human
UAP2-associated protein kinase 1
inhibitor
Human
UAbelson tyrosine-protein kinase 2
inhibitor
Human
UActivin receptor type-1
inhibitor
Human
UActivin receptor type-1B
inhibitor
Human
UAtypical kinase COQ8B, mitochondrial
inhibitor
Human
UALK tyrosine kinase receptor
inhibitor
Human
UAnkyrin repeat and protein kinase domain-containing protein 1
inhibitor
Human
UAurora kinase A
inhibitor
Human
UAurora kinase B
inhibitor
Human
UAurora kinase C
inhibitor
Human
UTyrosine-protein kinase receptor UFO
inhibitor
Human
UTyrosine-protein kinase Blk
inhibitor
Human
UBMP-2-inducible protein kinase
inhibitor
Human
UBone morphogenetic protein receptor type-1B
inhibitor
Human
UBone morphogenetic protein receptor type-2
inhibitor
Human
UCytoplasmic tyrosine-protein kinase BMX
inhibitor
Human
USerine/threonine-protein kinase B-raf
inhibitor
Human
UTyrosine-protein kinase BTK
inhibitor
Human
UCalcium/calmodulin-dependent protein kinase type 1
inhibitor
Human
UCalcium/calmodulin-dependent protein kinase type 1D
inhibitor
Human
UCalcium/calmodulin-dependent protein kinase type 1G
inhibitor
Human
UCalcium/calmodulin-dependent protein kinase type II subunit alpha
inhibitor
Human
UCalcium/calmodulin-dependent protein kinase type II subunit beta
inhibitor
Human
UCalcium/calmodulin-dependent protein kinase type II subunit delta
inhibitor
Human
UCalcium/calmodulin-dependent protein kinase type II subunit gamma
inhibitor
Human
UCalcium/calmodulin-dependent protein kinase kinase 1
inhibitor
Human
UCalcium/calmodulin-dependent protein kinase kinase 2
inhibitor
Human
UPeripheral plasma membrane protein CASK
inhibitor
Human
UKappa-casein
inhibitor
Human
UCyclin-dependent kinase 1
inhibitor
Human
USerine/threonine-protein kinase MRCK gamma
inhibitor
Human
UCyclin-dependent kinase 4
inhibitor
Human
UCyclin-dependent kinase-like 1
inhibitor
Human
UCyclin-dependent kinase-like 2
inhibitor
Human
USerine/threonine-protein kinase Chk1
inhibitor
Human
USerine/threonine-protein kinase Chk2
inhibitor
Human
UCitron Rho-interacting kinase
inhibitor
Human
UDual specificity protein kinase CLK1
inhibitor
Human
UDual specificity protein kinase CLK2
inhibitor
Human
UDual specificity protein kinase CLK3
inhibitor
Human
UDual specificity protein kinase CLK4
inhibitor
Human
UMacrophage colony-stimulating factor 1 receptor
inhibitor
Human
UTyrosine-protein kinase CSK
inhibitor
Human
UCasein kinase I isoform alpha
inhibitor
Human
UCasein kinase II subunit alpha
inhibitor
Human
UCasein kinase II subunit alpha'
inhibitor
Human
UDeath-associated protein kinase 1
inhibitor
Human
UDeath-associated protein kinase 2
inhibitor
Human
UDeath-associated protein kinase 3
inhibitor
Human
USerine/threonine-protein kinase DCLK1
inhibitor
Human
USerine/threonine-protein kinase DCLK2
inhibitor
Human
USerine/threonine-protein kinase DCLK3
inhibitor
Human
UEpithelial discoidin domain-containing receptor 1
inhibitor
Human
UDiscoidin domain-containing receptor 2
inhibitor
Human
UDual specificity tyrosine-phosphorylation-regulated kinase 1A
inhibitor
Human
UDual specificity tyrosine-phosphorylation-regulated kinase 1B
inhibitor
Human
UEpidermal growth factor receptor
inhibitor
Human
UEukaryotic translation initiation factor 2-alpha kinase 1
inhibitor
Human
UInterferon-induced, double-stranded RNA-activated protein kinase
inhibitor
Human
UeIF-2-alpha kinase GCN2
inhibitor
Human
UEphrin type-A receptor 1
inhibitor
Human
UEphrin type-A receptor 2
inhibitor
Human
UEphrin type-A receptor 3
inhibitor
Human
UEphrin type-A receptor 4
inhibitor
Human
UEphrin type-A receptor 5
inhibitor
Human
UEphrin type-A receptor 6
inhibitor
Human
UEphrin type-A receptor 7
inhibitor
Human
UEphrin type-A receptor 8
inhibitor
Human
UEphrin type-B receptor 1
inhibitor
Human
UEphrin type-B receptor 2
inhibitor
Human
UEphrin type-B receptor 4
inhibitor
Human
UEphrin type-B receptor 6
inhibitor
Human
UReceptor tyrosine-protein kinase erbB-2
inhibitor
Human
UReceptor tyrosine-protein kinase erbB-4
inhibitor
Human
USerine/threonine-protein kinase/endoribonuclease IRE1
inhibitor
Human
UTyrosine-protein kinase Fer
inhibitor
Human
UTyrosine-protein kinase Fes/Fps
inhibitor
Human
UFibroblast growth factor receptor 1
inhibitor
Human
UFibroblast growth factor receptor 2
inhibitor
Human
UFibroblast growth factor receptor 3
inhibitor
Human
UTyrosine-protein kinase Fgr
inhibitor
Human
UVascular endothelial growth factor receptor 1
inhibitor
Human
UReceptor-type tyrosine-protein kinase FLT3
inhibitor
Human
UVascular endothelial growth factor receptor 3
inhibitor
Human
USerine/threonine-protein kinase mTOR
inhibitor
Human
UTyrosine-protein kinase FRK
inhibitor
Human
UTyrosine-protein kinase Fyn
inhibitor
Human
UCyclin-G-associated kinase
inhibitor
Human
UGlycogen synthase kinase-3 alpha
inhibitor
Human
UGlycogen synthase kinase-3 beta
inhibitor
Human
UTyrosine-protein kinase HCK
inhibitor
Human
UHomeodomain-interacting protein kinase 2
inhibitor
Human
UHomeodomain-interacting protein kinase 3
inhibitor
Human
USerine/threonine-protein kinase ICK
inhibitor
Human
UInhibitor of nuclear factor kappa-B kinase subunit beta
inhibitor
Human
UInhibitor of nuclear factor kappa-B kinase subunit epsilon
inhibitor
Human
UInsulin receptor
inhibitor
Human
UInsulin receptor-related protein
inhibitor
Human
UInterleukin-1 receptor-associated kinase 1
inhibitor
Human
UInterleukin-1 receptor-associated kinase 3
inhibitor
Human
UInterleukin-1 receptor-associated kinase 4
inhibitor
Human
UTyrosine-protein kinase ITK/TSK
inhibitor
Human
UTyrosine-protein kinase JAK2
inhibitor
Human
UTyrosine-protein kinase JAK3
inhibitor
Human
UVascular endothelial growth factor receptor 2
inhibitor
Human
USerine/threonine-protein kinase SIK3
inhibitor
Human
UMast/stem cell growth factor receptor Kit
inhibitor
Human
USerine/threonine-protein kinase LATS1
inhibitor
Human
UTyrosine-protein kinase Lck
inhibitor
Human
ULIM domain kinase 1
inhibitor
Human
ULIM domain kinase 2
inhibitor
Human
ULeucine-rich repeat serine/threonine-protein kinase 2
inhibitor
Human
ULeukocyte tyrosine kinase receptor
inhibitor
Human
UTyrosine-protein kinase Lyn
inhibitor
Human
UDual specificity mitogen-activated protein kinase kinase 2
inhibitor
Human
UDual specificity mitogen-activated protein kinase kinase 3
inhibitor
Human
UDual specificity mitogen-activated protein kinase kinase 5
inhibitor
Human
UDual specificity mitogen-activated protein kinase kinase 6
inhibitor
Human
UMitogen-activated protein kinase kinase kinase 1
inhibitor
Human
UMitogen-activated protein kinase kinase kinase 10
inhibitor
Human
UMitogen-activated protein kinase kinase kinase 11
inhibitor
Human
UMitogen-activated protein kinase kinase kinase 12
inhibitor
Human
UMitogen-activated protein kinase kinase kinase 13
inhibitor
Human
UMitogen-activated protein kinase kinase kinase 15
inhibitor
Human
UMitogen-activated protein kinase kinase kinase 2
inhibitor
Human
UMitogen-activated protein kinase kinase kinase 3
inhibitor
Human
UMitogen-activated protein kinase kinase kinase 4
inhibitor
Human
UMitogen-activated protein kinase kinase kinase 6
inhibitor
Human
UMitogen-activated protein kinase kinase kinase 9
inhibitor
Human
UMitogen-activated protein kinase kinase kinase kinase 1
inhibitor
Human
UMitogen-activated protein kinase kinase kinase kinase 2
inhibitor
Human
UMitogen-activated protein kinase kinase kinase kinase 3
inhibitor
Human
UMitogen-activated protein kinase kinase kinase kinase 4
inhibitor
Human
UMitogen-activated protein kinase kinase kinase kinase 5
inhibitor
Human
UMitogen-activated protein kinase 10
inhibitor
Human
UMitogen-activated protein kinase 13
inhibitor
Human
UMitogen-activated protein kinase 14
inhibitor
Human
UMitogen-activated protein kinase 15
inhibitor
Human
UMitogen-activated protein kinase 4
inhibitor
Human
UMitogen-activated protein kinase 7
inhibitor
Human
UMitogen-activated protein kinase 9
inhibitor
Human
UMAP kinase-activated protein kinase 5
inhibitor
Human
USerine/threonine-protein kinase MARK1
inhibitor
Human
USerine/threonine-protein kinase MARK2
inhibitor
Human
UMAP/microtubule affinity-regulating kinase 3
inhibitor
Human
UMAP/microtubule affinity-regulating kinase 4
inhibitor
Human
UCLIP-associating protein 1
inhibitor
Human
UMicrotubule-associated serine/threonine-protein kinase 1
inhibitor
Human
UMegakaryocyte-associated tyrosine-protein kinase
inhibitor
Human
UMaternal embryonic leucine zipper kinase
inhibitor
Human
UTyrosine-protein kinase Mer
inhibitor
Human
UMisshapen-like kinase 1
inhibitor
Human
UMAP kinase-interacting serine/threonine-protein kinase 1
inhibitor
Human
UMAP kinase-interacting serine/threonine-protein kinase 2
inhibitor
Human
UMacrophage-stimulating protein receptor
inhibitor
Human
UMuscle, skeletal receptor tyrosine-protein kinase
inhibitor
Human
UMyosin light chain kinase, smooth muscle
inhibitor
Human
UMyosin light chain kinase 2, skeletal/cardiac muscle
inhibitor
Human
UMyosin light chain kinase 3
inhibitor
Human
UMyosin light chain kinase family member 4
inhibitor
Human
UMyosin-IIIa
inhibitor
Human
USerine/threonine-protein kinase Nek1
inhibitor
Human
USerine/threonine-protein kinase Nek11
inhibitor
Human
USerine/threonine-protein kinase Nek2
inhibitor
Human
USerine/threonine-protein kinase Nek3
inhibitor
Human
USerine/threonine-protein kinase Nek4
inhibitor
Human
USerine/threonine-protein kinase Nek5
inhibitor
Human
USerine/threonine-protein kinase Nek9
inhibitor
Human
UHigh affinity nerve growth factor receptor
inhibitor
Human
UBDNF/NT-3 growth factors receptor
inhibitor
Human
UNT-3 growth factor receptor
inhibitor
Human
UNUAK family SNF1-like kinase 1
inhibitor
Human
UNUAK family SNF1-like kinase 2
inhibitor
Human
USerine/threonine-protein kinase OSR1
inhibitor
Human
USerine/threonine-protein kinase PAK 1
inhibitor
Human
USerine/threonine-protein kinase PAK 2
inhibitor
Human
USerine/threonine-protein kinase PAK 3
inhibitor
Human
USerine/threonine-protein kinase PAK 4
inhibitor
Human
USerine/threonine-protein kinase PAK 6
inhibitor
Human
USerine/threonine-protein kinase PAK 5
inhibitor
Human
UCyclin-dependent kinase 16
inhibitor
Human
UCyclin-dependent kinase 17
inhibitor
Human
UPlatelet-derived growth factor receptor alpha
inhibitor
Human
UPlatelet-derived growth factor receptor beta
inhibitor
Human
U3-phosphoinositide-dependent protein kinase 1
inhibitor
Human
UCyclin-dependent kinase 15
inhibitor
Human
UPhosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform
inhibitor
Human
UPhosphatidylinositol 4-kinase beta
inhibitor
Human
UPhosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta
inhibitor
Human
UPhosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit gamma
inhibitor
Human
UPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
inhibitor
Human
UPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
inhibitor
Human
USerine/threonine-protein kinase pim-1
inhibitor
Human
USerine/threonine-protein kinase pim-3
inhibitor
Human
UPhosphatidylinositol 5-phosphate 4-kinase type-2 beta
inhibitor
Human
UPhosphatidylinositol 5-phosphate 4-kinase type-2 gamma
inhibitor
Human
UMembrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase
inhibitor
Human
USerine/threonine-protein kinase N1
inhibitor
Human
USerine/threonine-protein kinase N2
inhibitor
Human
USerine/threonine-protein kinase PLK1
inhibitor
Human
USerine/threonine-protein kinase PLK2
inhibitor
Human
USerine/threonine-protein kinase PLK3
inhibitor
Human
USerine/threonine-protein kinase PLK4
inhibitor
Human
U5'-AMP-activated protein kinase catalytic subunit alpha-1
inhibitor
Human
U5'-AMP-activated protein kinase
inhibitor
Human
UcAMP-dependent protein kinase catalytic subunit beta
inhibitor
Human
UProtein kinase C delta type
inhibitor
Human
UProtein kinase C epsilon type
inhibitor
Human
UProtein kinase C gamma type
inhibitor
Human
UProtein kinase C iota type
inhibitor
Human
UProtein kinase C theta type
inhibitor
Human
USerine/threonine-protein kinase D1
inhibitor
Human
UcGMP-dependent protein kinase 2
inhibitor
Human
USerine/threonine-protein kinase PRP4 homolog
inhibitor
Human
UFocal adhesion kinase 1
inhibitor
Human
UProtein-tyrosine kinase 2-beta
inhibitor
Human
UProtein-tyrosine kinase 6
inhibitor
Human
URAF proto-oncogene serine/threonine-protein kinase
inhibitor
Human
UProto-oncogene tyrosine-protein kinase receptor Ret
inhibitor
Human
USerine/threonine-protein kinase RIO1
inhibitor
Human
USerine/threonine-protein kinase RIO2
inhibitor
Human
USerine/threonine-protein kinase RIO3
inhibitor
Human
UReceptor-interacting serine/threonine-protein kinase 1
inhibitor
Human
UReceptor-interacting serine/threonine-protein kinase 2
inhibitor
Human
UReceptor-interacting serine/threonine-protein kinase 4
inhibitor
Human
URho-associated protein kinase 2
inhibitor
Human
UProto-oncogene tyrosine-protein kinase ROS
inhibitor
Human
URibosomal protein S6 kinase alpha-1
inhibitor
Human
URibosomal protein S6 kinase alpha-3
inhibitor
Human
USerine/threonine-protein kinase SBK1
inhibitor
Human
UUncharacterized serine/threonine-protein kinase SBK3
inhibitor
Human
USerine/threonine-protein kinase Sgk3
inhibitor
Human
USerine/threonine-protein kinase SIK1
inhibitor
Human
USerine/threonine-protein kinase SIK2
inhibitor
Human
USTE20-like serine/threonine-protein kinase
inhibitor
Human
USNF-related serine/threonine-protein kinase
inhibitor
Human
UProto-oncogene tyrosine-protein kinase Src
inhibitor
Human
UTyrosine-protein kinase Srms
inhibitor
Human
USerine/threonine-protein kinase 10
inhibitor
Human
USerine/threonine-protein kinase 16
inhibitor
Human
USerine/threonine-protein kinase 17A
inhibitor
Human
USerine/threonine-protein kinase 17B
inhibitor
Human
USerine/threonine-protein kinase 32A
inhibitor
Human
Absorption

Fostmatinib is the methylene phosphate prodrug of R406, the active metabolite [Label]. It is extensively hydrolyzed by intestinal alkaline phosphatase. Only negligible amounts of fostamatinib enter systemic circulation [6].

R406 has an absolute bioavailability of 55% and reaches peak plasma concentrations in approximately 1.5 h [6]. Administration with a high calorie, high fat meal increases exposure by 23% and the maximum plasma concentration by 15%. This may lengthen time to peak plasma concentration to approximately 3 h [6]. Exposure to R406 is known to be dose proportional up to 200 mg twice daily [Label]. R406 accumulates 2-3 fold with twice daily dosing at 100-160 mg.

Volume of distribution

R406 has an apparent oral volume of distribution of approximately 400 L [6].

Protein binding

R406 is 98.3% bound to plasma proteins [Label].

Metabolism

Fostamatinib is metabolized in the gut by alkaline phosphatase to the active metabolite R406 [Label]. R406 is further oxidized by CYP3A4 and glucuronidated by UGT1A9. Plasma metabolites found include an O-glucuronide conjugate, an N-glucuronide conjugate, an O-desmethyl metabolite, and a sulfate conjugate [Label]. A 3,5 benzene diol metabolite forms in the feces via processing of the O-desmethyl metabolite by gut bacteria [7].

Route of elimination

About 80% of R406 is excreted in the feces, primarily as the O-glucuronide conjugate and the O-desmethyl metabolite produced by gut bacteria [Label]. The remaining 20% is excreted in the urine as the N-glucuronide conjugate.

Half life

R406 has a half-life of elimination of approximately 15 h [6].

Clearance

R406 has an apparent oral clearance of approximately 300 mL/min [6].

Toxicity

Neither fostamatinib or R406 were found to be carcinogenic or mutagenic [Label]. Fostamatinib can cause embryo-fetal mortality or developmental abnormalities at exposures of 0.3-10 times the maximum recommended human dose.

Serious adverse effects include hypertension, neutropenia, diarrhea, and hepatotoxicity [Label]

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Fostamatinib.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Fostamatinib.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Fostamatinib.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Fostamatinib.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Fostamatinib.
6-Deoxyerythronolide BThe metabolism of Fostamatinib can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Fostamatinib.
AbacavirThe metabolism of Abacavir can be decreased when combined with Fostamatinib.
AbemaciclibFostamatinib may decrease the excretion rate of Abemaciclib which could result in a higher serum level.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Fostamatinib.
Food Interactions
Not Available

References

General References
  1. Riccaboni M, Bianchi I, Petrillo P: Spleen tyrosine kinases: biology, therapeutic targets and drugs. Drug Discov Today. 2010 Jul;15(13-14):517-30. doi: 10.1016/j.drudis.2010.05.001. Epub 2010 May 27. [PubMed:20553955]
  2. Braselmann S, Taylor V, Zhao H, Wang S, Sylvain C, Baluom M, Qu K, Herlaar E, Lau A, Young C, Wong BR, Lovell S, Sun T, Park G, Argade A, Jurcevic S, Pine P, Singh R, Grossbard EB, Payan DG, Masuda ES: R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation. J Pharmacol Exp Ther. 2006 Dec;319(3):998-1008. doi: 10.1124/jpet.106.109058. Epub 2006 Aug 31. [PubMed:16946104]
  3. Sanderson MP, Gelling SJ, Rippmann JF, Schnapp A: Comparison of the anti-allergic activity of Syk inhibitors with optimized Syk siRNAs in FcepsilonRI-activated RBL-2H3 basophilic cells. Cell Immunol. 2010;262(1):28-34. doi: 10.1016/j.cellimm.2009.12.004. Epub 2009 Dec 14. [PubMed:20053395]
  4. Sedlik C, Orbach D, Veron P, Schweighoffer E, Colucci F, Gamberale R, Ioan-Facsinay A, Verbeek S, Ricciardi-Castagnoli P, Bonnerot C, Tybulewicz VL, Di Santo J, Amigorena S: A critical role for Syk protein tyrosine kinase in Fc receptor-mediated antigen presentation and induction of dendritic cell maturation. J Immunol. 2003 Jan 15;170(2):846-52. [PubMed:12517949]
  5. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
  6. Baluom M, Grossbard EB, Mant T, Lau DT: Pharmacokinetics of fostamatinib, a spleen tyrosine kinase (SYK) inhibitor, in healthy human subjects following single and multiple oral dosing in three phase I studies. Br J Clin Pharmacol. 2013 Jul;76(1):78-88. doi: 10.1111/bcp.12048. [PubMed:23190017]
  7. Sweeny DJ, Li W, Clough J, Bhamidipati S, Singh R, Park G, Baluom M, Grossbard E, Lau DT: Metabolism of fostamatinib, the oral methylene phosphate prodrug of the spleen tyrosine kinase inhibitor R406 in humans: contribution of hepatic and gut bacterial processes to the overall biotransformation. Drug Metab Dispos. 2010 Jul;38(7):1166-76. doi: 10.1124/dmd.110.032151. Epub 2010 Apr 6. [PubMed:20371637]
  8. Fostamatinib FDA Approval [Link]
External Links
PubChem Compound
11671467
PubChem Substance
347828328
ChemSpider
9846198
BindingDB
50431381
ChEMBL
CHEMBL2103830
HET
2RC
Wikipedia
Fostamatinib
PDB Entries
4o75
FDA label
Download (549 KB)
MSDS
Download (179 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceAmount of Pioglitazone in Blood / Drug Drug Interaction (DDI) / Healthy Volunteers / Pharmacokinetics / Pioglitazone / Rheumatoid Arthritis1
1CompletedBasic ScienceAmount of R406 in Blood / Healthy Volunteers / Hepatic Impairment / Pharmacokinetics1
1CompletedBasic ScienceBioavailability / Pharmacokinetics1
1CompletedBasic ScienceHealthy Japanese Volunteers1
1CompletedBasic ScienceHealthy Volunteers2
1CompletedBasic ScienceHealthy Volunteers / Rheumatoid Arthritis3
1CompletedBasic ScienceImpaired Renal Function / Rheumatoid Arthritis1
1CompletedBasic ScienceLaymen Terminology Level of Oral Contraceptive in Blood, Oral Contraceptive, Rheumatoid Arthritis, Drug -Drug Interaction / Scientific Terminology Rheumatoid Arthritis, Healthy Female Volunteers, Pharmacokinetics, Oral Contraceptive, Drug-drug Interaction1
1CompletedBasic ScienceRheumatoid Arthritis1
1RecruitingTreatmentCancer of the Ovary1
1RecruitingTreatmentHaematological Malignancies1
1, 2CompletedTreatmentMalignant Lymphomas1
2Active Not RecruitingTreatmentIgA Nephropathy1
2Active Not RecruitingTreatmentWarm Antibody Autoimmune Hemolytic Anemia1
2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Neoplasms, Colorectal / Neoplasms, Head and Neck / Pheochromocytomas / Renal Cell Adenocarcinoma1
2CompletedTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
2CompletedTreatmentRheumatoid Arthritis3
2CompletedTreatmentT Cell Lymphomas1
2TerminatedTreatmentRheumatoid Arthritis5
2WithdrawnTreatmentIgA Nephropathy1
3Active Not RecruitingTreatmentImmune Thrombocytopenic Purpura ( ITP )1
3CompletedTreatmentImmune Thrombocytopenic Purpura ( ITP )2
3CompletedTreatmentRheumatoid Arthritis3
3TerminatedTreatmentRheumatoid Arthritis1
Not AvailableNo Longer AvailableNot AvailableImmune Thrombocytopenic Purpura ( ITP )1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral100 mg/1
TabletOral150 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8951504No2015-02-102032-07-27Us
US7989448No2011-08-022026-06-12Us
US9283238No2016-03-152026-06-17Us
US8912170No2014-12-162026-06-17Us
US8163902No2012-04-242026-06-17Us
US7538108No2009-05-262026-03-28Us
US9266912No2016-02-232026-01-19Us
US7449458No2008-11-112026-09-04Us
US9737554No2017-08-222026-01-19Us
US8211889No2012-07-032026-01-19Us
US8771648No2014-07-082032-07-27Us
US8445485No2013-05-212026-06-17Us
US8263122No2012-09-112030-11-24Us
US8652492No2014-02-182028-11-06Us

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.052 mg/mLALOGPS
logP2.78ALOGPS
logP1.46ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)1.46ChemAxon
pKa (Strongest Basic)2.71ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count13ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area186.72 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity137.1 m3·mol-1ChemAxon
Polarizability54.48 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as methoxyanilines. These are organic compound containing an aniline group substituted at one or more positions by a methoxy group.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Aniline and substituted anilines
Direct Parent
Methoxyanilines
Alternative Parents
Phenoxy compounds / Methoxybenzenes / Anisoles / Alkyl aryl ethers / Aminopyridines and derivatives / Monoalkyl phosphates / Aminopyrimidines and derivatives / Halopyrimidines / Imidolactams / Aryl fluorides
show 10 more
Substituents
Methoxyaniline / Anisole / Phenol ether / Methoxybenzene / Phenoxy compound / Halopyrimidine / Aminopyridine / Aminopyrimidine / Monoalkyl phosphate / Alkyl aryl ether
show 28 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
Curator comments
Drug binds with an IC50 of 50 nM and a Kd of 12 nM.
General Function
Receptor signaling protein tyrosine kinase activity
Specific Function
Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR). Regulates seve...
Gene Name
SYK
Uniprot ID
P43405
Uniprot Name
Tyrosine-protein kinase SYK
Molecular Weight
72065.76 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
  2. Braselmann S, Taylor V, Zhao H, Wang S, Sylvain C, Baluom M, Qu K, Herlaar E, Lau A, Young C, Wong BR, Lovell S, Sun T, Park G, Argade A, Jurcevic S, Pine P, Singh R, Grossbard EB, Payan DG, Masuda ES: R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation. J Pharmacol Exp Ther. 2006 Dec;319(3):998-1008. doi: 10.1124/jpet.106.109058. Epub 2006 Aug 31. [PubMed:16946104]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
Curator comments
Drug bound with an IC50 of 18-81 nM and a Ki of 17 nM.
General Function
G-protein coupled adenosine receptor activity
Specific Function
Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibits adenylyl cyclase. Possible role in reproduction.
Gene Name
ADORA3
Uniprot ID
P0DMS8
Uniprot Name
Adenosine receptor A3
Molecular Weight
36184.175 Da
References
  1. Braselmann S, Taylor V, Zhao H, Wang S, Sylvain C, Baluom M, Qu K, Herlaar E, Lau A, Young C, Wong BR, Lovell S, Sun T, Park G, Argade A, Jurcevic S, Pine P, Singh R, Grossbard EB, Payan DG, Masuda ES: R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation. J Pharmacol Exp Ther. 2006 Dec;319(3):998-1008. doi: 10.1124/jpet.106.109058. Epub 2006 Aug 31. [PubMed:16946104]
  2. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Studies only identified a monoamine transporter in general terms with no specific protein referenced. Drug bound with an IC50 of 1.96-2.74 μM and a Ki of 1.63 μM.
General Function
Not Available
Specific Function
Not Available
Gene Name
VMAT2
Uniprot ID
Q99870
Uniprot Name
Vesicle monoamine transporter type 2
Molecular Weight
17291.525 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
  2. Braselmann S, Taylor V, Zhao H, Wang S, Sylvain C, Baluom M, Qu K, Herlaar E, Lau A, Young C, Wong BR, Lovell S, Sun T, Park G, Argade A, Jurcevic S, Pine P, Singh R, Grossbard EB, Payan DG, Masuda ES: R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation. J Pharmacol Exp Ther. 2006 Dec;319(3):998-1008. doi: 10.1124/jpet.106.109058. Epub 2006 Aug 31. [PubMed:16946104]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Drug bound with an IC50 of 1.51 μM.
General Function
Fatty acid amide hydrolase activity
Specific Function
Degrades bioactive fatty acid amides like oleamide, the endogenous cannabinoid, anandamide and myristic amide to their corresponding acids, thereby serving to terminate the signaling functions of t...
Gene Name
FAAH
Uniprot ID
O00519
Uniprot Name
Fatty-acid amide hydrolase 1
Molecular Weight
63065.28 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Studies only identified an adenosine transporter in general terms with no reference to a specific protein. Drug bound with an IC50 of 1.84-1.86 μM and a Ki of 0.634 μM.
General Function
Nucleoside transmembrane transporter activity
Specific Function
Mediates both influx and efflux of nucleosides across the membrane (equilibrative transporter). It is sensitive (ES) to low concentrations of the inhibitor nitrobenzylmercaptopurine riboside (NBMPR...
Gene Name
SLC29A1
Uniprot ID
Q99808
Uniprot Name
Equilibrative nucleoside transporter 1
Molecular Weight
50218.805 Da
References
  1. Braselmann S, Taylor V, Zhao H, Wang S, Sylvain C, Baluom M, Qu K, Herlaar E, Lau A, Young C, Wong BR, Lovell S, Sun T, Park G, Argade A, Jurcevic S, Pine P, Singh R, Grossbard EB, Payan DG, Masuda ES: R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation. J Pharmacol Exp Ther. 2006 Dec;319(3):998-1008. doi: 10.1124/jpet.106.109058. Epub 2006 Aug 31. [PubMed:16946104]
  2. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Drug bound with an IC50 of 143 nM.
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Drug bound with an IC50 of 308 nM.
General Function
Metal ion binding
Specific Function
Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP (PubMed:9714779, ...
Gene Name
PDE5A
Uniprot ID
O76074
Uniprot Name
cGMP-specific 3',5'-cyclic phosphodiesterase
Molecular Weight
99984.14 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Drug bound with an IC50 of 5.5 μM.
General Function
Iron ion binding
Specific Function
Catalyzes the first step in leukotriene biosynthesis, and thereby plays a role in inflammatory processes.
Gene Name
ALOX5
Uniprot ID
P09917
Uniprot Name
Arachidonate 5-lipoxygenase
Molecular Weight
77982.595 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Drug bound with an IC50 of 11.9 μM.
General Function
Proteoglycan binding
Specific Function
Thiol protease. Key protease responsible for the removal of the invariant chain from MHC class II molecules. The bond-specificity of this proteinase is in part similar to the specificities of cathe...
Gene Name
CTSS
Uniprot ID
P25774
Uniprot Name
Cathepsin S
Molecular Weight
37495.49 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Drug bound with an IC50 of 5.93 μM.
General Function
Serpin family protein binding
Specific Function
Important for the overall degradation of proteins in lysosomes.
Gene Name
CTSL
Uniprot ID
P07711
Uniprot Name
Cathepsin L1
Molecular Weight
37563.97 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Drug binds with an IC50 of 1900 nM and Kd of 620 nM on the phosphorylated form . Binds with a Kd of 1120 nM on the non-phosphorylated form.
General Function
Syntaxin binding
Specific Function
Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility a...
Gene Name
ABL1
Uniprot ID
P00519
Uniprot Name
Tyrosine-protein kinase ABL1
Molecular Weight
122871.435 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Plasmodium falciparum (isolate 3D7)
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Calcium-dependent kinase which may phosphorylate proteins of the host erythrocyte membranes.
Specific Function
Atp binding
Gene Name
CPK1
Uniprot ID
P62344
Uniprot Name
Calcium-dependent protein kinase 1
Molecular Weight
60799.015 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Mycobacterium tuberculosis
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Drug binds with a Kd of 24 nM.
General Function
Protein kinase that regulates many aspects of mycobacterial physiology, and is critical for growth in vitro and survival of the pathogen in the host (PubMed:24706757). Is a key component of a signal transduction pathway that regulates cell growth, cell shape and cell division via phosphorylation of target proteins such as GarA, GlmU, PapA5, PbpA, FhaB (Rv0019c), FhaA (Rv0020c), MviN, PstP, EmbR, Rv1422, Rv1747 and RseA (PubMed:15978616, PubMed:15985609, PubMed:15987910, PubMed:16436437, PubMed:16817899, PubMed:16980473, PubMed:19121323, PubMed:19826007, PubMed:20025669, PubMed:21423706, PubMed:22275220). Also catalyzes the phosphorylation of the core proteasome alpha-subunit (PrcA), and thereby regulates the proteolytic activity of the proteasome (PubMed:25224505). Is a major regulator of the oxygen-dependent replication switch since PknB activity is necessary for reactivation of cells from the hypoxic state (PubMed:24409094). Shows a strong preference for Thr versus Ser as the phosphoacceptor. Overexpression of PknB alters cell morphology and leads to cell death (PubMed:24706757) (PubMed:24409094).
Specific Function
Atp binding
Gene Name
pknB
Uniprot ID
P9WI81
Uniprot Name
Serine/threonine-protein kinase PknB
Molecular Weight
66509.265 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Drug bind to both the protein kinase 1 and protein kinase 2 domains.
General Function
Constitutively active serine/threonine-protein kinase that exhibits growth-factor-independent kinase activity and that may participate in p53/TP53-dependent cell growth arrest signaling and play an inhibitory role during embryogenesis.
Specific Function
Atp binding
Gene Name
RPS6KA6
Uniprot ID
Q9UK32
Uniprot Name
Ribosomal protein S6 kinase alpha-6
Molecular Weight
83871.38 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Drug binds to both the catalytic domain and the pseudokinase domain.
General Function
Protein tyrosine kinase activity
Specific Function
Probably involved in intracellular signal transduction by being involved in the initiation of type I IFN signaling. Phosphorylates the interferon-alpha/beta receptor alpha chain.
Gene Name
TYK2
Uniprot ID
P29597
Uniprot Name
Non-receptor tyrosine-protein kinase TYK2
Molecular Weight
133648.77 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Drug binds with a Kd of 3.79 μM.
General Function
Atypical kinase involved in the biosynthesis of coenzyme Q, also named ubiquinone, an essential lipid-soluble electron transporter for aerobic cellular respiration (PubMed:25498144, PubMed:21296186, PubMed:25540914, PubMed:27499294). Its substrate specificity is unclear: does not show any protein kinase activity (PubMed:25498144, PubMed:27499294). Probably acts as a small molecule kinase, possibly a lipid kinase that phosphorylates a prenyl lipid in the ubiquinone biosynthesis pathway, as suggested by its ability to bind coenzyme Q lipid intermediates (PubMed:25498144, PubMed:27499294). Shows an unusual selectivity for binding ADP over ATP (PubMed:25498144).
Specific Function
Adp binding
Gene Name
COQ8A
Uniprot ID
Q8NI60
Uniprot Name
Atypical kinase COQ8A, mitochondrial
Molecular Weight
71949.52 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Drug bind to the catalytic domain with a Kd of 38 nM and the pseudokinase domain with a Kd of 1980 nM.
General Function
Ubiquitin protein ligase binding
Specific Function
Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway. Kinase partner for the interleukin (IL)-2 receptor.
Gene Name
JAK1
Uniprot ID
P23458
Uniprot Name
Tyrosine-protein kinase JAK1
Molecular Weight
133275.995 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Drug binds with an IC50 of 270 nM and a Kd of 520 nM.
General Function
Protein tyrosine kinase activity
Specific Function
Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including...
Gene Name
MET
Uniprot ID
P08581
Uniprot Name
Hepatocyte growth factor receptor
Molecular Weight
155540.035 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Drug binds with a Kd of 950 nM.
General Function
Not Available
Specific Function
Atp binding
Gene Name
NIM1K
Uniprot ID
Q8IY84
Uniprot Name
Serine/threonine-protein kinase NIM1
Molecular Weight
49605.705 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Mediator of cell growth. Modulates apoptosis.
Gene Name
STK26
Uniprot ID
Q9P289
Uniprot Name
Serine/threonine-protein kinase 26
Molecular Weight
46528.395 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Drug binds with an IC50 of 700 nM and a Kd of 490 nM.
General Function
Ubiquitin protein ligase binding
Specific Function
Phosphorylates a large number of substrates in the cytoplasm and the nucleus. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which bin...
Gene Name
PRKACA
Uniprot ID
P17612
Uniprot Name
cAMP-dependent protein kinase catalytic subunit alpha
Molecular Weight
40589.38 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine-protein kinase that acts on both serine and threonine residues and promotes apoptosis in response to stress stimuli and caspase activation. Mediates oxidative-stress-induced cell death by modulating phosphorylation of JNK1-JNK2 (MAPK8 and MAPK9), p38 (MAPK11, MAPK12, MAPK13 and MAPK14) during oxidative stress. Plays a role in a staurosporine-induced caspase-independent apoptotic pathway by regulating the nuclear translocation of AIFM1 and ENDOG and the DNase activity associated with ENDOG. Phosphorylates STK38L on 'Thr-442' and stimulates its kinase activity. In association with STK26 negatively regulates Golgi reorientation in polarized cell migration upon RHO activation (PubMed:27807006). Regulates also cellular migration with alteration of PTPN12 activity and PXN phosphorylation: phosphorylates PTPN12 and inhibits its activity and may regulate PXN phosphorylation through PTPN12. May act as a key regulator of axon regeneration in the optic nerve and radial nerve.
Specific Function
Atp binding
Gene Name
STK24
Uniprot ID
Q9Y6E0
Uniprot Name
Serine/threonine-protein kinase 24
Molecular Weight
49307.45 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. STK3/MST2 and STK4/MST1 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation. Phosphorylates NKX2-1 (By similarity). Phosphorylates NEK2 and plays a role in centrosome disjunction by regulating the localization of NEK2 to centrosome, and its ability to phosphorylate CROCC and CEP250. In conjunction with SAV1, activates the transcriptional activity of ESR1 through the modulation of its phosphorylation. Positively regulates RAF1 activation via suppression of the inhibitory phosphorylation of RAF1 on 'Ser-259'. Phosphorylates MOBKL1A and RASSF2. Phosphorylates MOBKL1B on 'Thr-74'. Acts cooperatively with MOBKL1B to activate STK38.
Specific Function
Atp binding
Gene Name
STK3
Uniprot ID
Q13188
Uniprot Name
Serine/threonine-protein kinase 3
Molecular Weight
56300.69 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Drug binds with an IC50 of 100 nM and a Kd of 760 nM.
General Function
Non-receptor tyrosine kinase that contributes to signaling from many receptors and participates as a signal transducer in multiple downstream pathways, including regulation of the actin cytoskeleton. Plays a redundant role to ITK in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. Required for TCR-dependent IL2 gene induction. Phosphorylates DOK1, one CD28-specific substrate, and contributes to CD28-signaling. Mediates signals that negatively regulate IL2RA expression induced by TCR cross-linking. Plays a redundant role to BTK in BCR-signaling for B-cell development and activation, especially by phosphorylating STAP1, a BCR-signaling protein. Required in mast cells for efficient cytokine production. Involved in both growth and differentiation mechanisms of myeloid cells through activation by the granulocyte colony-stimulating factor CSF3, a critical cytokine to promoting the growth, differentiation, and functional activation of myeloid cells. Participates in platelet signaling downstream of integrin activation. Cooperates with JAK2 through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. GRB10, a negative modifier of the FOS activation pathway, is another substrate of TEC. TEC is involved in G protein-coupled receptor- and integrin-mediated signalings in blood platelets. Plays a role in hepatocyte proliferation and liver regeneration and is involved in HGF-induced ERK signaling pathway. TEC regulates also FGF2 unconventional secretion (endoplasmic reticulum (ER)/Golgi-independent mechanism) under various physiological conditions through phosphorylation of FGF2 'Tyr-215'. May also be involved in the regulation of osteoclast differentiation.
Specific Function
Atp binding
Gene Name
TEC
Uniprot ID
P42680
Uniprot Name
Tyrosine-protein kinase Tec
Molecular Weight
73580.73 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine protein kinase which phosphorylates VIME. May play a specific role in the dynamic behavior of the intermediate filament cytoskeleton by phosphorylation of VIME (By similarity). Not essential for the survival of KRAS-dependent AML cell lines.
Specific Function
Atp binding
Gene Name
STK33
Uniprot ID
Q9BYT3
Uniprot Name
Serine/threonine-protein kinase 33
Molecular Weight
57830.355 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Not Available
Specific Function
Atp binding
Gene Name
STK35
Uniprot ID
Q8TDR2
Uniprot Name
Serine/threonine-protein kinase 35
Molecular Weight
58050.755 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine protein kinase which plays an important role in the sonic hedgehog (Shh) pathway by regulating the activity of GLI transcription factors (PubMed:10806483). Controls the activity of the transcriptional regulators GLI1, GLI2 and GLI3 by opposing the effect of SUFU and promoting their nuclear localization (PubMed:10806483). GLI2 requires an additional function of STK36 to become transcriptionally active, but the enzyme does not need to possess an active kinase catalytic site for this to occur (PubMed:10806483). Required for postnatal development, possibly by regulating the homeostasis of cerebral spinal fluid or ciliary function (By similarity). Essential for construction of the central pair apparatus of motile cilia.
Specific Function
Atp binding
Gene Name
STK36
Uniprot ID
Q9NRP7
Uniprot Name
Serine/threonine-protein kinase 36
Molecular Weight
143993.57 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Negative regulator of MAP3K1/2 signaling. Converts MAP3K2 from its phosphorylated form to its non-phosphorylated form and inhibits autophosphorylation of MAP3K2.
Specific Function
Atp binding
Gene Name
STK38
Uniprot ID
Q15208
Uniprot Name
Serine/threonine-protein kinase 38
Molecular Weight
54189.77 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Involved in the regulation of structural processes in differentiating and mature neuronal cells.
Specific Function
Actin binding
Gene Name
STK38L
Uniprot ID
Q9Y2H1
Uniprot Name
Serine/threonine-protein kinase 38-like
Molecular Weight
54002.425 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
May act as a mediator of stress-activated signals. Mediates the inhibition of SLC4A4, SLC26A6 as well as CFTR activities by the WNK scaffolds, probably through phosphorylation.
Specific Function
Atp binding
Gene Name
STK39
Uniprot ID
Q9UEW8
Uniprot Name
STE20/SPS1-related proline-alanine-rich protein kinase
Molecular Weight
59473.46 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine-protein kinase involved in various processes such as p38/MAPK14 stress-activated MAPK cascade, DNA damage response and regulation of cytoskeleton stability. Phosphorylates MAP2K3, MAP2K6 and MARK2. Acts as an activator of the p38/MAPK14 stress-activated MAPK cascade by mediating phosphorylation and subsequent activation of the upstream MAP2K3 and MAP2K6 kinases. Involved in G-protein coupled receptor signaling to p38/MAPK14. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress-activated MAPK cascade, probably by mediating phosphorylation of MAP2K3 and MAP2K6. Acts as a regulator of cytoskeleton stability by phosphorylating 'Thr-208' of MARK2, leading to activate MARK2 kinase activity and subsequent phosphorylation and detachment of MAPT/TAU from microtubules. Also acts as a regulator of apoptosis: regulates apoptotic morphological changes, including cell contraction, membrane blebbing and apoptotic bodies formation via activation of the MAPK8/JNK cascade.
Specific Function
Atp binding
Gene Name
TAOK1
Uniprot ID
Q7L7X3
Uniprot Name
Serine/threonine-protein kinase TAO1
Molecular Weight
116069.56 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Serine/threonine-protein kinase involved in different processes such as membrane blebbing and apoptotic bodies formation DNA damage response and MAPK14/p38 MAPK stress-activated MAPK cascade. Phosp...
Gene Name
TAOK2
Uniprot ID
Q9UL54
Uniprot Name
Serine/threonine-protein kinase TAO2
Molecular Weight
138250.17 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine-protein kinase that acts as a regulator of the p38/MAPK14 stress-activated MAPK cascade and of the MAPK8/JNK cascade. Acts as an activator of the p38/MAPK14 stress-activated MAPK cascade. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress-activated MAPK cascade, probably by mediating phosphorylation of upstream MAP2K3 and MAP2K6 kinases. Inhibits basal activity of MAPK8/JNK cascade and diminishes its activation in response epidermal growth factor (EGF).
Specific Function
Atp binding
Gene Name
TAOK3
Uniprot ID
Q9H2K8
Uniprot Name
Serine/threonine-protein kinase TAO3
Molecular Weight
105405.165 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents. Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the IRFs leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNA and IFNB. In order to establish such an antiviral state, TBK1 form several different complexes whose composition depends on the type of cell and cellular stimuli. Thus, several scaffolding molecules including FADD, TRADD, MAVS, AZI2, TANK or TBKBP1/SINTBAD can be recruited to the TBK1-containing-complexes. Under particular conditions, functions as a NF-kappa-B effector by phosphorylating NF-kappa-B inhibitor alpha/NFKBIA, IKBKB or RELA to translocate NF-Kappa-B to the nucleus. Restricts bacterial proliferation by phosphorylating the autophagy receptor OPTN/Optineurin on 'Ser-177', thus enhancing LC3 binding affinity and antibacterial autophagy (PubMed:21617041). Phosphorylates SMCR8 component of the C9orf72-SMCR8 complex, promoting autophagosome maturation (PubMed:27103069). Phosphorylates and activates AKT1 (PubMed:21464307). Seems to play a role in energy balance regulation by sustaining a state of chronic, low-grade inflammation in obesity, wich leads to a negative impact on insulin sensitivity. Attenuates retroviral budding by phosphorylating the endosomal sorting complex required for transport-I (ESCRT-I) subunit VPS37C (PubMed:21270402). Phosphorylates Borna disease virus (BDV) P protein (PubMed:16155125).
Specific Function
Atp binding
Gene Name
TBK1
Uniprot ID
Q9UHD2
Uniprot Name
Serine/threonine-protein kinase TBK1
Molecular Weight
83641.51 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for ANGPT1, ANGPT2 and ANGPT4 and regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading...
Gene Name
TEK
Uniprot ID
Q02763
Uniprot Name
Angiopoietin-1 receptor
Molecular Weight
125829.005 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Dual specificity protein kinase activity catalyzing autophosphorylation and phosphorylation of exogenous substrates on both serine/threonine and tyrosine residues. Probably plays a central role at and after the meiotic phase of spermatogenesis (By similarity).
Specific Function
Atp binding
Gene Name
TESK1
Uniprot ID
Q15569
Uniprot Name
Dual specificity testis-specific protein kinase 1
Molecular Weight
67683.685 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Type ii transforming growth factor beta receptor binding
Specific Function
Transmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine kinase receptor, TGFBR2, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Tra...
Gene Name
TGFBR1
Uniprot ID
P36897
Uniprot Name
TGF-beta receptor type-1
Molecular Weight
55959.18 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Type iii transforming growth factor beta receptor binding
Specific Function
Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Tran...
Gene Name
TGFBR2
Uniprot ID
P37173
Uniprot Name
TGF-beta receptor type-2
Molecular Weight
64567.1 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transmembrane tyrosine-protein kinase that may modulate TEK/TIE2 activity and contribute to the regulation of angiogenesis.
Specific Function
Atp binding
Gene Name
TIE1
Uniprot ID
P35590
Uniprot Name
Tyrosine-protein kinase receptor Tie-1
Molecular Weight
125088.595 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Rapidly and transiently inhibited by phosphorylation following the generation of DNA double-stranded breaks during S-phase. This is cell cycle checkpoint and ATM-pathway dependent and appears to regulate processes involved in chromatin assembly. Isoform 3 phosphorylates and enhances the stability of the t-SNARE SNAP23, augmenting its assembly with syntaxin. Isoform 3 protects the cells from the ionizing radiation by facilitating the repair of DSBs. In vitro, phosphorylates histone H3 at 'Ser-10'.
Specific Function
Atp binding
Gene Name
TLK1
Uniprot ID
Q9UKI8
Uniprot Name
Serine/threonine-protein kinase tousled-like 1
Molecular Weight
86698.925 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine-protein kinase involved in the process of chromatin assembly and probably also DNA replication, transcription, repair, and chromosome segregation. Phosphorylates the chromatin assembly factors ASF1A AND ASF1B. Phosphorylation of ASF1A prevents its proteasome-mediated degradation, thereby enhancing chromatin assembly. Negative regulator of amino acid starvation-induced autophagy.
Specific Function
Atp binding
Gene Name
TLK2
Uniprot ID
Q86UE8
Uniprot Name
Serine/threonine-protein kinase tousled-like 2
Molecular Weight
87660.305 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine kinase that acts as an essential activator of the Wnt signaling pathway. Recruited to promoters of Wnt target genes and required to activate their expression. May act by phosphorylating TCF4/TCF7L2. Appears to act upstream of the JUN N-terminal pathway. May play a role in the response to environmental stress. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. More generally, it may play a role in cytoskeletal rearrangements and regulate cell spreading. Phosphorylates SMAD1 on Thr-322.
Specific Function
Atp binding
Gene Name
TNIK
Uniprot ID
Q9UKE5
Uniprot Name
TRAF2 and NCK-interacting protein kinase
Molecular Weight
154942.115 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Involved in negative regulation of cell growth. Has tumor suppressor properties. Plays a negative regulatory role in the Ras-MAPK pathway. May function in signaling pathways utilized broadly during fetal development and more selectively in adult tissues and in cells of the lymphohematopoietic system. Could specifically be involved in phospholipid signal transduction.
Specific Function
Atp binding
Gene Name
TNK1
Uniprot ID
Q13470
Uniprot Name
Non-receptor tyrosine-protein kinase TNK1
Molecular Weight
72466.995 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Ww domain binding
Specific Function
Non-receptor tyrosine-protein and serine/threonine-protein kinase that is implicated in cell spreading and migration, cell survival, cell growth and proliferation. Transduces extracellular signals ...
Gene Name
TNK2
Uniprot ID
Q07912
Uniprot Name
Activated CDC42 kinase 1
Molecular Weight
114567.605 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
May play a role in cardiac physiology.
Specific Function
Atp binding
Gene Name
TNNI3K
Uniprot ID
Q59H18
Uniprot Name
Serine/threonine-protein kinase TNNI3K
Molecular Weight
92849.73 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Testis-specific serine/threonine-protein kinase required during spermatid development. Phosphorylates 'Ser-288' of TSKS. Involved in the late stages of spermatogenesis, during the reconstruction of the cytoplasm. During spermatogenesis, required for the transformation of a ring-shaped structure around the base of the flagellum originating from the chromatoid body.
Specific Function
Atp binding
Gene Name
TSSK1B
Uniprot ID
Q9BXA7
Uniprot Name
Testis-specific serine/threonine-protein kinase 1
Molecular Weight
41617.53 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Phosphorylates proteins on serine, threonine, and tyrosine. Probably associated with cell proliferation. Essential for chromosome alignment by enhancing AURKB activity (via direct CDCA8 phosphoryla...
Gene Name
TTK
Uniprot ID
P33981
Uniprot Name
Dual specificity protein kinase TTK
Molecular Weight
97071.5 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Non-receptor tyrosine kinase that plays a redundant role with ITK in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. When antigen presenting cells (APC) activate T-cell receptor (TCR), a series of phosphorylation lead to the recruitment of TXK to the cell membrane, where it is phosphorylated at Tyr-420. Phosphorylation leads to TXK full activation. Contributes also to signaling from many receptors and participates in multiple downstream pathways, including regulation of the actin cytoskeleton. Like ITK, can phosphorylate PLCG1, leading to its localization in lipid rafts and activation, followed by subsequent cleavage of its substrates. In turn, the endoplasmic reticulum releases calcium in the cytoplasm and the nuclear activator of activated T-cells (NFAT) translocates into the nucleus to perform its transcriptional duty. With PARP1 and EEF1A1, TXK forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFNG to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production. Phosphorylates both PARP1 and EEF1A1. Phosphorylates also key sites in LCP2 leading to the up-regulation of Th1 preferred cytokine IL-2. Phosphorylates 'Tyr-201' of CTLA4 which leads to the association of PI-3 kinase with the CTLA4 receptor.
Specific Function
Atp binding
Gene Name
TXK
Uniprot ID
P42681
Uniprot Name
Tyrosine-protein kinase TXK
Molecular Weight
61257.9 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including TULP1 or GAS6. Regulates many physiological processes including cell survival, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of TYRO3 on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with PIK3R1 and thereby enhances PI3-kinase activity. Activates the AKT survival pathway, including nuclear translocation of NF-kappa-B and up-regulation of transcription of NF-kappa-B-regulated genes. TYRO3 signaling plays a role in various processes such as neuron protection from excitotoxic injury, platelet aggregation and cytoskeleton reorganization. Plays also an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3.
Specific Function
Atp binding
Gene Name
TYRO3
Uniprot ID
Q06418
Uniprot Name
Tyrosine-protein kinase receptor TYRO3
Molecular Weight
96904.425 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine-protein kinase involved in autophagy in response to starvation. Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes. Part of regulatory feedback loops in autophagy: acts both as a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR. Activated via phosphorylation by AMPK and also acts as a regulator of AMPK by mediating phosphorylation of AMPK subunits PRKAA1, PRKAB2 and PRKAG1, leading to negatively regulate AMPK activity. May phosphorylate ATG13/KIAA0652 and RPTOR; however such data need additional evidences. Plays a role early in neuronal differentiation and is required for granule cell axon formation. May also phosphorylate SESN2 and SQSTM1 to regulate autophagy (PubMed:25040165).
Specific Function
Atp binding
Gene Name
ULK1
Uniprot ID
O75385
Uniprot Name
Serine/threonine-protein kinase ULK1
Molecular Weight
112630.155 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine-protein kinase involved in autophagy in response to starvation. Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes. Part of regulatory feedback loops in autophagy: acts both as a downstream effector and a negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR. Activated via phosphorylation by AMPK, also acts as a negative regulator of AMPK through phosphorylation of the AMPK subunits PRKAA1, PRKAB2 and PRKAG1. May phosphorylate ATG13/KIAA0652, FRS2, FRS3 and RPTOR; however such data need additional evidences. Not involved in ammonia-induced autophagy or in autophagic response of cerebellar granule neurons (CGN) to low potassium concentration. Plays a role early in neuronal differentiation and is required for granule cell axon formation: may govern axon formation via Ras-like GTPase signaling and through regulation of the Rab5-mediated endocytic pathways within developing axons.
Specific Function
Atp binding
Gene Name
ULK2
Uniprot ID
Q8IYT8
Uniprot Name
Serine/threonine-protein kinase ULK2
Molecular Weight
112693.175 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine protein kinase that acts as a regulator of Sonic hedgehog (SHH) signaling and autophagy. Acts as a negative regulator of SHH signaling in the absence of SHH ligand: interacts with SUFU, thereby inactivating the protein kinase activity and preventing phosphorylation of GLI proteins (GLI1, GLI2 and/or GLI3). Positively regulates SHH signaling in the presence of SHH: dissociates from SUFU, autophosphorylates and mediates phosphorylation of GLI2, activating it and promoting its nuclear translocation. Phosphorylates in vitro GLI2, as well as GLI1 and GLI3, although less efficiently. Also acts as a regulator of autophagy: following cellular senescence, able to induce autophagy.
Specific Function
Atp binding
Gene Name
ULK3
Uniprot ID
Q6PHR2
Uniprot Name
Serine/threonine-protein kinase ULK3
Molecular Weight
53443.885 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Acts as a negative regulator of entry into mitosis (G2 to M transition) by protecting the nucleus from cytoplasmically activated cyclin B1-complexed CDK1 before the onset of mitosis by mediating ph...
Gene Name
WEE1
Uniprot ID
P30291
Uniprot Name
Wee1-like protein kinase
Molecular Weight
71596.655 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Receptor binding
Specific Function
Non-receptor protein tyrosine kinase that is involved in the regulation of cell growth and survival, apoptosis, cell-cell adhesion, cytoskeleton remodeling, and differentiation. Stimulation by rece...
Gene Name
YES1
Uniprot ID
P07947
Uniprot Name
Tyrosine-protein kinase Yes
Molecular Weight
60800.78 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Not Available
Specific Function
Atp binding
Gene Name
MAP3K19
Uniprot ID
Q56UN5
Uniprot Name
Mitogen-activated protein kinase kinase kinase 19
Molecular Weight
150536.265 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Stress-activated component of a protein kinase signal transduction cascade. Regulates the JNK and p38 pathways. Pro-apoptotic. Role in regulation of S and G2 cell cycle checkpoint by direct phospho...
Gene Name
ZAK
Uniprot ID
Q9NYL2
Uniprot Name
Mitogen-activated protein kinase kinase kinase MLT
Molecular Weight
91154.315 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Receptor binding
Specific Function
Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates motility, adhesion and cytokine expression of mature T-cells, as well as thymocyte development....
Gene Name
ZAP70
Uniprot ID
P43403
Uniprot Name
Tyrosine-protein kinase ZAP-70
Molecular Weight
69871.63 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Regulates clathrin-mediated endocytosis by phosphorylating the AP2M1/mu2 subunit of the adaptor protein complex 2 (AP-2) which ensures high affinity binding of AP-2 to cargo membrane proteins during the initial stages of endocytosis. Isoform 1 and isoform 2 display similar levels of kinase activity towards AP2M1. Regulates phosphorylation of other AP-2 subunits as well as AP-2 localization and AP-2-mediated internalization of ligand complexes. Phosphorylates NUMB and regulates its cellular localization, promoting NUMB localization to endosomes. Binds to and stabilizes the activated form of NOTCH1, increases its localization in endosomes and regulates its transcriptional activity.
Specific Function
Ap-2 adaptor complex binding
Gene Name
AAK1
Uniprot ID
Q2M2I8
Uniprot Name
AP2-associated protein kinase 1
Molecular Weight
103884.3 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Receptor binding
Specific Function
Non-receptor tyrosine-protein kinase that plays an ABL1-overlapping role in key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, ce...
Gene Name
ABL2
Uniprot ID
P42684
Uniprot Name
Abelson tyrosine-protein kinase 2
Molecular Weight
128341.935 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transmembrane receptor protein serine/threonine kinase activity
Specific Function
On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which auto...
Gene Name
ACVR1
Uniprot ID
Q04771
Uniprot Name
Activin receptor type-1
Molecular Weight
57152.41 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Ubiquitin protein ligase binding
Specific Function
Transmembrane serine/threonine kinase activin type-1 receptor forming an activin receptor complex with activin receptor type-2 (ACVR2A or ACVR2B). Transduces the activin signal from the cell surfac...
Gene Name
ACVR1B
Uniprot ID
P36896
Uniprot Name
Activin receptor type-1B
Molecular Weight
56806.05 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Atypical kinase involved in the biosynthesis of coenzyme Q, also named ubiquinone, an essential lipid-soluble electron transporter for aerobic cellular respiration (PubMed:24270420). Its substrate specificity is unclear: does not show any protein kinase activity. Probably acts as a small molecule kinase, possibly a lipid kinase that phosphorylates a prenyl lipid in the ubiquinone biosynthesis pathway. Required for podocyte migration (PubMed:24270420).
Specific Function
Atp binding
Gene Name
COQ8B
Uniprot ID
Q96D53
Uniprot Name
Atypical kinase COQ8B, mitochondrial
Molecular Weight
60068.925 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Neuronal orphan receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis a...
Gene Name
ALK
Uniprot ID
Q9UM73
Uniprot Name
ALK tyrosine kinase receptor
Molecular Weight
176440.535 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Not Available
Specific Function
Atp binding
Gene Name
ANKK1
Uniprot ID
Q8NFD2
Uniprot Name
Ankyrin repeat and protein kinase domain-containing protein 1
Molecular Weight
84631.68 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein serine/threonine/tyrosine kinase activity
Specific Function
Mitotic serine/threonine kinases that contributes to the regulation of cell cycle progression. Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role i...
Gene Name
AURKA
Uniprot ID
O14965
Uniprot Name
Aurora kinase A
Molecular Weight
45809.03 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein serine/threonine/tyrosine kinase activity
Specific Function
Serine/threonine-protein kinase component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in...
Gene Name
AURKB
Uniprot ID
Q96GD4
Uniprot Name
Aurora kinase B
Molecular Weight
39310.195 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein serine/threonine/tyrosine kinase activity
Specific Function
Serine/threonine-protein kinase component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in...
Gene Name
AURKC
Uniprot ID
Q9UQB9
Uniprot Name
Aurora kinase C
Molecular Weight
35590.91 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding growth factor GAS6 and which is thus regulating many physiological processes including cell survival, cell proliferation, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of AXL. Following activation by ligand, ALX binds and induces tyrosine phosphorylation of PI3-kinase subunits PIK3R1, PIK3R2 and PIK3R3; but also GRB2, PLCG1, LCK and PTPN11. Other downstream substrate candidates for AXL are CBL, NCK2, SOCS1 and TNS2. Recruitment of GRB2 and phosphatidylinositol 3 kinase regulatory subunits by AXL leads to the downstream activation of the AKT kinase. GAS6/AXL signaling plays a role in various processes such as endothelial cell survival during acidification by preventing apoptosis, optimal cytokine signaling during human natural killer cell development, hepatic regeneration, gonadotropin-releasing hormone neuron survival and migration, platelet activation, or regulation of thrombotic responses. Plays also an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response.
Specific Function
Atp binding
Gene Name
AXL
Uniprot ID
P30530
Uniprot Name
Tyrosine-protein kinase receptor UFO
Molecular Weight
98335.965 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling. B-cell receptor (BCR) signaling requires a tight regulation of several protein tyrosine kinases and phosphatases, and associated coreceptors. Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation. Signaling through BLK plays an important role in transmitting signals through surface immunoglobulins and supports the pro-B to pre-B transition, as well as the signaling for growth arrest and apoptosis downstream of B-cell receptor. Specifically binds and phosphorylates CD79A at 'Tyr-188'and 'Tyr-199', as well as CD79B at 'Tyr-196' and 'Tyr-207'. Phosphorylates also the immunoglobulin G receptors FCGR2A, FCGR2B and FCGR2C. With FYN and LYN, plays an essential role in pre-B-cell receptor (pre-BCR)-mediated NF-kappa-B activation. Contributes also to BTK activation by indirectly stimulating BTK intramolecular autophosphorylation. In pancreatic islets, acts as a modulator of beta-cells function through the up-regulation of PDX1 and NKX6-1 and consequent stimulation of insulin secretion in response to glucose.
Specific Function
Atp binding
Gene Name
BLK
Uniprot ID
P51451
Uniprot Name
Tyrosine-protein kinase Blk
Molecular Weight
57706.01 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
May be involved in osteoblast differentiation.
Specific Function
Ap-2 adaptor complex binding
Gene Name
BMP2K
Uniprot ID
Q9NSY1
Uniprot Name
BMP-2-inducible protein kinase
Molecular Weight
129170.91 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for BMP7/OP-1 and GDF5. Positively regulates chondrocyte differentiation through GDF5 interaction.
Specific Function
Atp binding
Gene Name
BMPR1B
Uniprot ID
O00238
Uniprot Name
Bone morphogenetic protein receptor type-1B
Molecular Weight
56929.905 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Binds to BMP7, BMP2 and, less efficiently, BMP4. Binding is weak but enhanced by the presence of type I receptors for BMPs. Mediates induction of adipogenesis by GDF6.
Specific Function
Activin receptor activity, type ii
Gene Name
BMPR2
Uniprot ID
Q13873
Uniprot Name
Bone morphogenetic protein receptor type-2
Molecular Weight
115200.475 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Non-receptor tyrosine kinase that plays central but diverse modulatory roles in various signaling processes involved in the regulation of actin reorganization, cell migration, cell proliferation and survival, cell adhesion, and apoptosis. Participates in signal transduction stimulated by growth factor receptors, cytokine receptors, G-protein coupled receptors, antigen receptors and integrins. Induces tyrosine phosphorylation of BCAR1 in response to integrin regulation. Activation of BMX by integrins is mediated by PTK2/FAK1, a key mediator of integrin signaling events leading to the regulation of actin cytoskeleton and cell motility. Plays a critical role in TNF-induced angiogenesis, and implicated in the signaling of TEK and FLT1 receptors, 2 important receptor families essential for angiogenesis. Required for the phosphorylation and activation of STAT3, a transcription factor involved in cell differentiation. Also involved in interleukin-6 (IL6) induced differentiation. Plays also a role in programming adaptive cytoprotection against extracellular stress in different cell systems, salivary epithelial cells, brain endothelial cells, and dermal fibroblasts. May be involved in regulation of endocytosis through its interaction with an endosomal protein RUFY1. May also play a role in the growth and differentiation of hematopoietic cells; as well as in signal transduction in endocardial and arterial endothelial cells.
Specific Function
Atp binding
Gene Name
BMX
Uniprot ID
P51813
Uniprot Name
Cytoplasmic tyrosine-protein kinase BMX
Molecular Weight
78010.17 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May play a role in the postsynaptic responses of hippocampal neuron. Phosphorylates MAP2K1, a...
Gene Name
BRAF
Uniprot ID
P15056
Uniprot Name
Serine/threonine-protein kinase B-raf
Molecular Weight
84436.135 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling. Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately le...
Gene Name
BTK
Uniprot ID
Q06187
Uniprot Name
Tyrosine-protein kinase BTK
Molecular Weight
76280.71 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium influx, regulates transcription activators activity, cell cycle, hormone production, cell differentiation, actin filament organization and neurite outgrowth. Recognizes the substrate consensus sequence [MVLIF]-x-R-x(2)-[ST]-x(3)-[MVLIF]. Regulates axonal extension and growth cone motility in hippocampal and cerebellar nerve cells. Upon NMDA receptor-mediated Ca(2+) elevation, promotes dendritic growth in hippocampal neurons and is essential in synapses for full long-term potentiation (LTP) and ERK2-dependent translational activation. Downstream of NMDA receptors, promotes the formation of spines and synapses in hippocampal neurons by phosphorylating ARHGEF7/BETAPIX on 'Ser-694', which results in the enhancement of ARHGEF7 activity and activation of RAC1. Promotes neuronal differentiation and neurite outgrowth by activation and phosphorylation of MARK2 on 'Ser-91', 'Ser-92', 'Ser-93' and 'Ser-294'. Promotes nuclear export of HDAC5 and binding to 14-3-3 by phosphorylation of 'Ser-259' and 'Ser-498' in the regulation of muscle cell differentiation. Regulates NUMB-mediated endocytosis by phosphorylation of NUMB on 'Ser-276' and 'Ser-295'. Involved in the regulation of basal and estrogen-stimulated migration of medulloblastoma cells through ARHGEF7/BETAPIX phosphorylation (By similarity). Is required for proper activation of cyclin-D1/CDK4 complex during G1 progression in diploid fibroblasts. Plays a role in K(+) and ANG2-mediated regulation of the aldosterone synthase (CYP11B2) to produce aldosterone in the adrenal cortex. Phosphorylates EIF4G3/eIF4GII. In vitro phosphorylates CREB1, ATF1, CFTR, MYL9 and SYN1/synapsin I.
Specific Function
Atp binding
Gene Name
CAMK1
Uniprot ID
Q14012
Uniprot Name
Calcium/calmodulin-dependent protein kinase type 1
Molecular Weight
41336.705 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Calmodulin-dependent protein kinase activity
Specific Function
Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium influx, activates CREB-dependent gene transcription, regulates cal...
Gene Name
CAMK1D
Uniprot ID
Q8IU85
Uniprot Name
Calcium/calmodulin-dependent protein kinase type 1D
Molecular Weight
42913.36 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Calmodulin-dependent protein kinase activity
Specific Function
Calcium/calmodulin-dependent protein kinase belonging to a proposed calcium-triggered signaling cascade. In vitro phosphorylates transcription factor CREB1 (By similarity).
Gene Name
CAMK1G
Uniprot ID
Q96NX5
Uniprot Name
Calcium/calmodulin-dependent protein kinase type 1G
Molecular Weight
53086.475 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
CaM-kinase II (CAMK2) is a prominent kinase in the central nervous system that may function in long-term potentiation and neurotransmitter release. Member of the NMDAR signaling complex in excitato...
Gene Name
CAMK2A
Uniprot ID
Q9UQM7
Uniprot Name
Calcium/calmodulin-dependent protein kinase type II subunit alpha
Molecular Weight
54087.265 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein homodimerization activity
Specific Function
Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in dendritic spine and synapse formation, neuronal p...
Gene Name
CAMK2B
Uniprot ID
Q13554
Uniprot Name
Calcium/calmodulin-dependent protein kinase type II subunit beta
Molecular Weight
72677.055 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Titin binding
Specific Function
Calcium/calmodulin-dependent protein kinase involved in the regulation of Ca(2+) homeostatis and excitation-contraction coupling (ECC) in heart by targeting ion channels, transporters and accessory...
Gene Name
CAMK2D
Uniprot ID
Q13557
Uniprot Name
Calcium/calmodulin-dependent protein kinase type II subunit delta
Molecular Weight
56368.94 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein homodimerization activity
Specific Function
Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in sarcoplsamic reticulum Ca(2+) transport in skelet...
Gene Name
CAMK2G
Uniprot ID
Q13555
Uniprot Name
Calcium/calmodulin-dependent protein kinase type II subunit gamma
Molecular Weight
62608.655 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Calcium/calmodulin-dependent protein kinase that belongs to a proposed calcium-triggered signaling cascade involved in a number of cellular processes. Phosphorylates CAMK1, CAMK1D, CAMK1G and CAMK4. Involved in regulating cell apoptosis. Promotes cell survival by phosphorylating AKT1/PKB that inhibits pro-apoptotic BAD/Bcl2-antagonist of cell death.
Specific Function
Atp binding
Gene Name
CAMKK1
Uniprot ID
Q8N5S9
Uniprot Name
Calcium/calmodulin-dependent protein kinase kinase 1
Molecular Weight
55734.96 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Calcium/calmodulin-dependent protein kinase belonging to a proposed calcium-triggered signaling cascade involved in a number of cellular processes. Isoform 1, isoform 2 and isoform 3 phosphorylate CAMK1 and CAMK4. Isoform 3 phosphorylates CAMK1D. Isoform 4, isoform 5 and isoform 6 lacking part of the calmodulin-binding domain are inactive. Efficiently phosphorylates 5'-AMP-activated protein kinase (AMPK) trimer, including that consisting of PRKAA1, PRKAB1 and PRKAG1. This phosphorylation is stimulated in response to Ca(2+) signals (By similarity). Seems to be involved in hippocampal activation of CREB1 (By similarity). May play a role in neurite growth. Isoform 3 may promote neurite elongation, while isoform 1 may promoter neurite branching.
Specific Function
Atp binding
Gene Name
CAMKK2
Uniprot ID
Q96RR4
Uniprot Name
Calcium/calmodulin-dependent protein kinase kinase 2
Molecular Weight
64745.215 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Multidomain scaffolding protein with a role in synaptic transmembrane protein anchoring and ion channel trafficking. Contributes to neural development and regulation of gene expression via interact...
Gene Name
CASK
Uniprot ID
O14936
Uniprot Name
Peripheral plasma membrane protein CASK
Molecular Weight
105121.915 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Kappa-casein stabilizes micelle formation, preventing casein precipitation in milk.
Specific Function
Not Available
Gene Name
CSN3
Uniprot ID
P07498
Uniprot Name
Kappa-casein
Molecular Weight
20305.135 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Rna polymerase ii carboxy-terminal domain kinase activity
Specific Function
Plays a key role in the control of the eukaryotic cell cycle by modulating the centrosome cycle as well as mitotic onset; promotes G2-M transition, and regulates G1 progress and G1-S transition via...
Gene Name
CDK1
Uniprot ID
P06493
Uniprot Name
Cyclin-dependent kinase 1
Molecular Weight
34095.14 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
May act as a downstream effector of CDC42 in cytoskeletal reorganization. Contributes to the actomyosin contractility required for cell invasion, through the regulation of MYPT1 and thus MLC2 phosphorylation (By similarity).
Specific Function
Atp binding
Gene Name
CDC42BPG
Uniprot ID
Q6DT37
Uniprot Name
Serine/threonine-protein kinase MRCK gamma
Molecular Weight
172457.57 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Cyclin-dependent protein serine/threonine kinase regulator activity
Specific Function
Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S tra...
Gene Name
CDK4
Uniprot ID
P11802
Uniprot Name
Cyclin-dependent kinase 4
Molecular Weight
33729.55 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Not Available
Specific Function
Atp binding
Gene Name
CDKL1
Uniprot ID
Q00532
Uniprot Name
Cyclin-dependent kinase-like 1
Molecular Weight
41802.175 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Not Available
Specific Function
Atp binding
Gene Name
CDKL2
Uniprot ID
Q92772
Uniprot Name
Cyclin-dependent kinase-like 2
Molecular Weight
56018.1 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA. May also nega...
Gene Name
CHEK1
Uniprot ID
O14757
Uniprot Name
Serine/threonine-protein kinase Chk1
Molecular Weight
54433.115 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Ubiquitin protein ligase binding
Specific Function
Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks. May also...
Gene Name
CHEK2
Uniprot ID
O96017
Uniprot Name
Serine/threonine-protein kinase Chk2
Molecular Weight
60914.26 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Plays a role in cytokinesis. Required for KIF14 localization to the central spindle and midbody. Putative RHO/RAC effector that binds to the GTP-bound forms of RHO and RAC1. It probably binds p21 with a tighter specificity in vivo. Displays serine/threonine protein kinase activity. Plays an important role in the regulation of cytokinesis and the development of the central nervous system. Phosphorylates MYL9/MLC2.
Specific Function
Atp binding
Gene Name
CIT
Uniprot ID
O14578
Uniprot Name
Citron Rho-interacting kinase
Molecular Weight
231428.95 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein serine/threonine/tyrosine kinase activity
Specific Function
Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex and may be a constitue...
Gene Name
CLK1
Uniprot ID
P49759
Uniprot Name
Dual specificity protein kinase CLK1
Molecular Weight
57290.145 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex. May be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing and can cause redistribution of SR proteins from speckles to a diffuse nucleoplasmic distribution. Acts as a suppressor of hepatic gluconeogenesis and glucose output by repressing PPARGC1A transcriptional activity on gluconeogenic genes via its phosphorylation. Phosphorylates PPP2R5B thereby stimulating the assembly of PP2A phosphatase with the PPP2R5B-AKT1 complex leading to dephosphorylation of AKT1. Phosphorylates: PTPN1, SRSF1 and SRSF3. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells.
Specific Function
Atp binding
Gene Name
CLK2
Uniprot ID
P49760
Uniprot Name
Dual specificity protein kinase CLK2
Molecular Weight
60089.64 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex. May be a constituent ...
Gene Name
CLK3
Uniprot ID
P49761
Uniprot Name
Dual specificity protein kinase CLK3
Molecular Weight
73514.365 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex and may be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing. Phosphorylates SRSF1 and SRSF3. Required for the regulation of alternative splicing of MAPT/TAU. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells.
Specific Function
Atp binding
Gene Name
CLK4
Uniprot ID
Q9HAZ1
Uniprot Name
Dual specificity protein kinase CLK4
Molecular Weight
57491.51 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein homodimerization activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for CSF1 and IL34 and plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor ...
Gene Name
CSF1R
Uniprot ID
P07333
Uniprot Name
Macrophage colony-stimulating factor 1 receptor
Molecular Weight
107982.955 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Receptor binding
Specific Function
Non-receptor tyrosine-protein kinase that plays an important role in the regulation of cell growth, differentiation, migration and immune response. Phosphorylates tyrosine residues located in the C...
Gene Name
CSK
Uniprot ID
P41240
Uniprot Name
Tyrosine-protein kinase CSK
Molecular Weight
50703.975 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. It can phosphorylate a large number of proteins. Participates in Wnt signaling. Phosphorylates CTNNB1 at 'Ser-45'. May phosphorylate PER1 and PER2. May play a role in segregating chromosomes during mitosis (PubMed:11955436, PubMed:1409656, PubMed:18305108). May play a role in keratin cytoskeleton disassembly and thereby, it may regulate epithelial cell migration (PubMed:23902688).
Specific Function
Atp binding
Gene Name
CSNK1A1
Uniprot ID
P48729
Uniprot Name
Casein kinase I isoform alpha
Molecular Weight
38914.59 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Catalytic subunit of a constitutively active serine/threonine-protein kinase complex that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated ser...
Gene Name
CSNK2A1
Uniprot ID
P68400
Uniprot Name
Casein kinase II subunit alpha
Molecular Weight
45143.25 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Catalytic subunit of a constitutively active serine/threonine-protein kinase complex that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated ser...
Gene Name
CSNK2A2
Uniprot ID
P19784
Uniprot Name
Casein kinase II subunit alpha'
Molecular Weight
41212.925 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Syntaxin-1 binding
Specific Function
Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. Regulates both type I apoptotic and type ...
Gene Name
DAPK1
Uniprot ID
P53355
Uniprot Name
Death-associated protein kinase 1
Molecular Weight
160044.615 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. Regulates both type I apoptotic and type II autophagic cell death signals, depending on the cellular setting. The former is caspase-dependent, while the latter is caspase-independent and is characterized by the accumulation of autophagic vesicles. Acts as a mediator of anoikis and a suppressor of beta-catenin-dependent anchorage-independent growth of malignant epithelial cells. May play a role in granulocytic maturation (PubMed:17347302). Regulates granulocytic motility by controlling cell spreading and polarization (PubMed:24163421).
Specific Function
Atp binding
Gene Name
DAPK2
Uniprot ID
Q9UIK4
Uniprot Name
Death-associated protein kinase 2
Molecular Weight
42897.685 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Rho gtpase binding
Specific Function
Serine/threonine kinase which is involved in the regulation of apoptosis, autophagy, transcription, translation and actin cytoskeleton reorganization. Involved in the regulation of smooth muscle co...
Gene Name
DAPK3
Uniprot ID
O43293
Uniprot Name
Death-associated protein kinase 3
Molecular Weight
52535.165 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Probable kinase that may be involved in a calcium-signaling pathway controlling neuronal migration in the developing brain. May also participate in functions of the mature nervous system.
Specific Function
Atp binding
Gene Name
DCLK1
Uniprot ID
O15075
Uniprot Name
Serine/threonine-protein kinase DCLK1
Molecular Weight
82223.215 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein kinase with a significantly reduced C(a2+)/CAM affinity and dependence compared to other members of the CaMK family. May play a role in the down-regulation of CRE-dependent gene activation probably by phosphorylation of the CREB coactivator CRTC2/TORC2 and the resulting retention of TORC2 in the cytoplasm (By similarity).
Specific Function
Atp binding
Gene Name
DCLK2
Uniprot ID
Q8N568
Uniprot Name
Serine/threonine-protein kinase DCLK2
Molecular Weight
83604.885 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Not Available
Specific Function
Atp binding
Gene Name
DCLK3
Uniprot ID
Q9C098
Uniprot Name
Serine/threonine-protein kinase DCLK3
Molecular Weight
73813.755 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Tyrosine kinase that functions as cell surface receptor for fibrillar collagen and regulates cell attachment to the extracellular matrix, remodeling of the extracellular matrix, cell migration, dif...
Gene Name
DDR1
Uniprot ID
Q08345
Uniprot Name
Epithelial discoidin domain-containing receptor 1
Molecular Weight
101126.72 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Tyrosine kinase that functions as cell surface receptor for fibrillar collagen and regulates cell differentiation, remodeling of the extracellular matrix, cell migration and cell proliferation. Req...
Gene Name
DDR2
Uniprot ID
Q16832
Uniprot Name
Discoidin domain-containing receptor 2
Molecular Weight
96735.44 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Tau protein binding
Specific Function
May play a role in a signaling pathway regulating nuclear functions of cell proliferation. Modulates alternative splicing by phosphorylating the splice factor SRSF6 (By similarity). Phosphorylates ...
Gene Name
DYRK1A
Uniprot ID
Q13627
Uniprot Name
Dual specificity tyrosine-phosphorylation-regulated kinase 1A
Molecular Weight
85583.41 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities. Enhances the transcriptional activity of TCF1/HNF1A and FOXO1. Inhibits epithelial cell migration. Mediates colon carcinoma cell survival in mitogen-poor environments. Inhibits the SHH and WNT1 pathways, thereby enhancing adipogenesis. In addition, promotes expression of the gluconeogenic enzyme glucose-6-phosphatase (G6PC).
Specific Function
Atp binding
Gene Name
DYRK1B
Uniprot ID
Q9Y463
Uniprot Name
Dual specificity tyrosine-phosphorylation-regulated kinase 1B
Molecular Weight
69197.19 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Ubiquitin protein ligase binding
Specific Function
Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TG...
Gene Name
EGFR
Uniprot ID
P00533
Uniprot Name
Epidermal growth factor receptor
Molecular Weight
134276.185 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Inhibits protein synthesis at the translation initiation level, in response to various stress conditions, including oxidative stress, heme deficiency, osmotic shock and heat shock. Exerts its function through the phosphorylation of EIF2S1 at 'Ser-48' and 'Ser-51', thus preventing its recycling. Binds hemin forming a 1:1 complex through a cysteine thiolate and histidine nitrogenous coordination. This binding occurs with moderate affinity, allowing it to sense the heme concentration within the cell. Thanks to this unique heme-sensing capacity, plays a crucial role to shut off protein synthesis during acute heme-deficient conditions. In red blood cells (RBCs), controls hemoglobin synthesis ensuring a coordinated regulation of the synthesis of its heme and globin moieties. Thus plays an essential protective role for RBC survival in anemias of iron deficiency. Similarly, in hepatocytes, involved in heme-mediated translational control of CYP2B and CYP3A and possibly other hepatic P450 cytochromes. May also contain ER stress during acute heme-deficient conditions (By similarity).
Specific Function
Atp binding
Gene Name
EIF2AK1
Uniprot ID
Q9BQI3
Uniprot Name
Eukaryotic translation initiation factor 2-alpha kinase 1
Molecular Weight
71105.915 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
IFN-induced dsRNA-dependent serine/threonine-protein kinase which plays a key role in the innate immune response to viral infection and is also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation. Exerts its antiviral activity on a wide range of DNA and RNA viruses including hepatitis C virus (HCV), hepatitis B virus (HBV), measles virus (MV) and herpes simplex virus 1 (HHV-1). Inhibits viral replication via phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (EIF2S1), this phosphorylation impairs the recycling of EIF2S1 between successive rounds of initiation leading to inhibition of translation which eventually results in shutdown of cellular and viral protein synthesis. Also phosphorylates other substrates including p53/TP53, PPP2R5A, DHX9, ILF3, IRS1 and the HHV-1 viral protein US11. In addition to serine/threonine-protein kinase activity, also has tyrosine-protein kinase activity and phosphorylates CDK1 at 'Tyr-4' upon DNA damage, facilitating its ubiquitination and proteosomal degradation. Either as an adapter protein and/or via its kinase activity, can regulate various signaling pathways (p38 MAP kinase, NF-kappa-B and insulin signaling pathways) and transcription factors (JUN, STAT1, STAT3, IRF1, ATF3) involved in the expression of genes encoding proinflammatory cytokines and IFNs. Activates the NF-kappa-B pathway via interaction with IKBKB and TRAF family of proteins and activates the p38 MAP kinase pathway via interaction with MAP2K6. Can act as both a positive and negative regulator of the insulin signaling pathway (ISP). Negatively regulates ISP by inducing the inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) at 'Ser-312' and positively regulates ISP via phosphorylation of PPP2R5A which activates FOXO1, which in turn up-regulates the expression of insulin receptor substrate 2 (IRS2). Can regulate NLRP3 inflammasome assembly and the activation of NLRP3, NLRP1, AIM2 and NLRC4 inflammasomes. Can trigger apoptosis via FADD-mediated activation of CASP8. Plays a role in the regulation of the cytoskeleton by binding to gelsolin (GSN), sequestering the protein in an inactive conformation away from actin.
Specific Function
Atp binding
Gene Name
EIF2AK2
Uniprot ID
P19525
Uniprot Name
Interferon-induced, double-stranded RNA-activated protein kinase
Molecular Weight
62093.71 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2-alpha/EIF2S1) on 'Ser-52' in response to low amino acid availability (PubMed:25329545). Plays a role as an activator of the integrated stress response (ISR) required for adapatation to amino acid starvation. Converts phosphorylated eIF-2-alpha/EIF2S1 either to a competitive inhibitor of the translation initiation factor eIF-2B, leading to a global protein synthesis repression, and thus to a reduced overall utilization of amino acids, or to a translational initiation activation of specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion. Binds uncharged tRNAs (By similarity). Involved in cell cycle arrest by promoting cyclin D1 mRNA translation repression after the unfolded protein response pathway (UPR) activation or cell cycle inhibitor CDKN1A/p21 mRNA translation activation in response to amino acid deprivation (PubMed:26102367). Plays a role in the consolidation of synaptic plasticity, learning as well as formation of long-term memory. Plays a role in neurite outgrowth inhibition. Plays a proapoptotic role in response to glucose deprivation. Promotes global cellular protein synthesis repression in response to UV irradiation independently of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 MAPK signaling pathways (By similarity). Plays a role in the antiviral response against alphavirus infection; impairs early viral mRNA translation of the incoming genomic virus RNA, thus preventing alphavirus replication (By similarity).
Specific Function
Atp binding
Gene Name
EIF2AK4
Uniprot ID
Q9P2K8
Uniprot Name
eIF-2-alpha kinase GCN2
Molecular Weight
186908.89 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Binds with a low affinity EFNA3 and EFNA4 and with a high affinity to EFNA1 which most probably constitutes its cognate/functional ligand. Upon activation by EFNA1 induces cell attachment to the extracellular matrix inhibiting cell spreading and motility through regulation of ILK and downstream RHOA and RAC. Plays also a role in angiogenesis and regulates cell proliferation. May play a role in apoptosis.
Specific Function
Atp binding
Gene Name
EPHA1
Uniprot ID
P21709
Uniprot Name
Ephrin type-A receptor 1
Molecular Weight
108126.305 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. Th...
Gene Name
EPHA2
Uniprot ID
P29317
Uniprot Name
Ephrin type-A receptor 2
Molecular Weight
108265.585 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Highly promiscuous for ephrin-A ligands it binds preferentially EFNA5. Upon activation by EFNA5 regulates cell-cell adhesion, cytoskeletal organization and cell migration. Plays a role in cardiac cells migration and differentiation and regulates the formation of the atrioventricular canal and septum during development probably through activation by EFNA1. Involved in the retinotectal mapping of neurons. May also control the segregation but not the guidance of motor and sensory axons during neuromuscular circuit development.
Specific Function
Atp binding
Gene Name
EPHA3
Uniprot ID
P29320
Uniprot Name
Ephrin type-A receptor 3
Molecular Weight
110129.68 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Receptor tyrosine kinase which binds membrane-bound ephrin family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Highly promiscuous, it has the unique property among Eph receptors to bind and to be physiologically activated by both GPI-anchored ephrin-A and transmembrane ephrin-B ligands including EFNA1 and EFNB3. Upon activation by ephrin ligands, modulates cell morphology and integrin-dependent cell adhesion through regulation of the Rac, Rap and Rho GTPases activity. Plays an important role in the development of the nervous system controlling different steps of axonal guidance including the establishment of the corticospinal projections. May also control the segregation of motor and sensory axons during neuromuscular circuit development. In addition to its role in axonal guidance plays a role in synaptic plasticity. Activated by EFNA1 phosphorylates CDK5 at 'Tyr-15' which in turn phosphorylates NGEF regulating RHOA and dendritic spine morphogenesis. In the nervous system, plays also a role in repair after injury preventing axonal regeneration and in angiogenesis playing a role in central nervous system vascular formation. Additionally, its promiscuity makes it available to participate in a variety of cell-cell signaling regulating for instance the development of the thymic epithelium.
Specific Function
Atp binding
Gene Name
EPHA4
Uniprot ID
P54764
Uniprot Name
Ephrin type-A receptor 4
Molecular Weight
109859.065 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transmembrane-ephrin receptor activity
Specific Function
Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The ...
Gene Name
EPHA5
Uniprot ID
P54756
Uniprot Name
Ephrin type-A receptor 5
Molecular Weight
114802.31 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling (By similarity).
Specific Function
Atp binding
Gene Name
EPHA6
Uniprot ID
Q9UF33
Uniprot Name
Ephrin type-A receptor 6
Molecular Weight
116378.465 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The ...
Gene Name
EPHA7
Uniprot ID
Q15375
Uniprot Name
Ephrin type-A receptor 7
Molecular Weight
112095.765 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. The GPI-anchored ephrin-A EFNA2, EFNA3, and EFNA5 are able to activate EPHA8 through phosphorylation. With EFNA5 may regulate integrin-mediated cell adhesion and migration on fibronectin substrate but also neurite outgrowth. During development of the nervous system plays also a role in axon guidance. Downstream effectors of the EPHA8 signaling pathway include FYN which promotes cell adhesion upon activation by EPHA8 and the MAP kinases in the stimulation of neurite outgrowth (By similarity).
Specific Function
Atp binding
Gene Name
EPHA8
Uniprot ID
P29322
Uniprot Name
Ephrin type-A receptor 8
Molecular Weight
111001.57 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Cognate/functional ephrin ligands for this receptor include EFNB1, EFNB2 and EFNB3. During nervous system development, regulates retinal axon guidance redirecting ipsilaterally ventrotemporal retinal ganglion cells axons at the optic chiasm midline. This probably requires repulsive interaction with EFNB2. In the adult nervous system together with EFNB3, regulates chemotaxis, proliferation and polarity of the hippocampus neural progenitors. In addition to its role in axon guidance plays also an important redundant role with other ephrin-B receptors in development and maturation of dendritic spines and synapse formation. May also regulate angiogenesis. More generally, may play a role in targeted cell migration and adhesion. Upon activation by EFNB1 and probably other ephrin-B ligands activates the MAPK/ERK and the JNK signaling cascades to regulate cell migration and adhesion respectively. Involved in the maintenance of the pool of satellite cells (muscle stem cells) by promoting their self-renewal and reducing their activation and differentiation (By similarity).
Specific Function
Atp binding
Gene Name
EPHB1
Uniprot ID
P54762
Uniprot Name
Ephrin type-B receptor 1
Molecular Weight
109884.175 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transmembrane-ephrin receptor activity
Specific Function
Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The...
Gene Name
EPHB2
Uniprot ID
P29323
Uniprot Name
Ephrin type-B receptor 2
Molecular Weight
117491.74 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The...
Gene Name
EPHB4
Uniprot ID
P54760
Uniprot Name
Ephrin type-B receptor 4
Molecular Weight
108269.26 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Kinase-defective receptor for members of the ephrin-B family. Binds to ephrin-B1 and ephrin-B2. Modulates cell adhesion and migration by exerting both positive and negative effects upon stimulation with ephrin-B2. Inhibits JNK activation, T-cell receptor-induced IL-2 secretion and CD25 expression upon stimulation with ephrin-B2.
Specific Function
Atp binding
Gene Name
EPHB6
Uniprot ID
O15197
Uniprot Name
Ephrin type-B receptor 6
Molecular Weight
110699.39 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transmembrane signaling receptor activity
Specific Function
Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, alt...
Gene Name
ERBB2
Uniprot ID
P04626
Uniprot Name
Receptor tyrosine-protein kinase erbB-2
Molecular Weight
137909.27 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mamma...
Gene Name
ERBB4
Uniprot ID
Q15303
Uniprot Name
Receptor tyrosine-protein kinase erbB-4
Molecular Weight
146806.865 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Senses unfolded proteins in the lumen of the endoplasmic reticulum via its N-terminal domain which leads to enzyme auto-activation. The active endoribonuclease domain splices XBP1 mRNA to generate ...
Gene Name
ERN1
Uniprot ID
O75460
Uniprot Name
Serine/threonine-protein kinase/endoribonuclease IRE1
Molecular Weight
109734.08 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Tyrosine-protein kinase that acts downstream of cell surface receptors for growth factors and plays a role in the regulation of the actin cytoskeleton, microtubule assembly, lamellipodia formation, cell adhesion, cell migration and chemotaxis. Acts downstream of EGFR, KIT, PDGFRA and PDGFRB. Acts downstream of EGFR to promote activation of NF-kappa-B and cell proliferation. May play a role in the regulation of the mitotic cell cycle. Plays a role in the insulin receptor signaling pathway and in activation of phosphatidylinositol 3-kinase. Acts downstream of the activated FCER1 receptor and plays a role in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Plays a role in the regulation of mast cell degranulation. Plays a role in leukocyte recruitment and diapedesis in response to bacterial lipopolysaccharide (LPS). Plays a role in synapse organization, trafficking of synaptic vesicles, the generation of excitatory postsynaptic currents and neuron-neuron synaptic transmission. Plays a role in neuronal cell death after brain damage. Phosphorylates CTTN, CTNND1, PTK2/FAK1, GAB1, PECAM1 and PTPN11. May phosphorylate JUP and PTPN1. Can phosphorylate STAT3, but the biological relevance of this depends on cell type and stimulus.
Specific Function
Atp binding
Gene Name
FER
Uniprot ID
P16591
Uniprot Name
Tyrosine-protein kinase Fer
Molecular Weight
94637.255 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Tyrosine-protein kinase that acts downstream of cell surface receptors and plays a role in the regulation of the actin cytoskeleton, microtubule assembly, cell attachment and cell spreading. Plays a role in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Acts down-stream of the activated FCER1 receptor and the mast/stem cell growth factor receptor KIT. Plays a role in the regulation of mast cell degranulation. Plays a role in the regulation of cell differentiation and promotes neurite outgrowth in response to NGF signaling. Plays a role in cell scattering and cell migration in response to HGF-induced activation of EZR. Phosphorylates BCR and down-regulates BCR kinase activity. Phosphorylates HCLS1/HS1, PECAM1, STAT3 and TRIM28.
Specific Function
Atp binding
Gene Name
FES
Uniprot ID
P07332
Uniprot Name
Tyrosine-protein kinase Fes/Fps
Molecular Weight
93495.875 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation ...
Gene Name
FGFR1
Uniprot ID
P11362
Uniprot Name
Fibroblast growth factor receptor 1
Molecular Weight
91866.935 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosi...
Gene Name
FGFR2
Uniprot ID
P21802
Uniprot Name
Fibroblast growth factor receptor 2
Molecular Weight
92024.29 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis. Plays an...
Gene Name
FGFR3
Uniprot ID
P22607
Uniprot Name
Fibroblast growth factor receptor 3
Molecular Weight
87708.905 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors devoid of kinase activity and contributes to the regulation of immune responses, including neutrophil, monocy...
Gene Name
FGR
Uniprot ID
P09769
Uniprot Name
Tyrosine-protein kinase Fgr
Molecular Weight
59478.11 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Vegf-b-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell ...
Gene Name
FLT1
Uniprot ID
P17948
Uniprot Name
Vascular endothelial growth factor receptor 1
Molecular Weight
150767.185 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells...
Gene Name
FLT3
Uniprot ID
P36888
Uniprot Name
Receptor-type tyrosine-protein kinase FLT3
Molecular Weight
112902.51 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardi...
Gene Name
FLT4
Uniprot ID
P35916
Uniprot Name
Vascular endothelial growth factor receptor 3
Molecular Weight
152755.94 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Tfiiic-class transcription factor binding
Specific Function
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals. MTOR directly...
Gene Name
MTOR
Uniprot ID
P42345
Uniprot Name
Serine/threonine-protein kinase mTOR
Molecular Weight
288889.05 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Receptor binding
Specific Function
Non-receptor tyrosine-protein kinase that negatively regulates cell proliferation. Positively regulates PTEN protein stability through phosphorylation of PTEN on 'Tyr-336', which in turn prevents i...
Gene Name
FRK
Uniprot ID
P42685
Uniprot Name
Tyrosine-protein kinase FRK
Molecular Weight
58253.61 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Non-receptor tyrosine-protein kinase that plays a role in many biological processes including regulation of cell growth and survival, cell adhesion, integrin-mediated signaling, cytoskeletal remode...
Gene Name
FYN
Uniprot ID
P06241
Uniprot Name
Tyrosine-protein kinase Fyn
Molecular Weight
60761.49 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Associates with cyclin G and CDK5. Seems to act as an auxilin homolog that is involved in the uncoating of clathrin-coated vesicles by Hsc70 in non-neuronal cells. Expression oscillates slightly during the cell cycle, peaking at G1.
Specific Function
Atp binding
Gene Name
GAK
Uniprot ID
O14976
Uniprot Name
Cyclin-G-associated kinase
Molecular Weight
143189.16 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), CTNNB1/beta-catenin, APC and AXIN1. Requires primed phosphorylation of the majority of its substrates. Contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. Regulates glycogen metabolism in liver, but not in muscle. May also mediate the development of insulin resistance by regulating activation of transcription factors. In Wnt signaling, regulates the level and transcriptional activity of nuclear CTNNB1/beta-catenin. Facilitates amyloid precursor protein (APP) processing and the generation of APP-derived amyloid plaques found in Alzheimer disease. May be involved in the regulation of replication in pancreatic beta-cells. Is necessary for the establishment of neuronal polarity and axon outgrowth. Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation.
Specific Function
Atp binding
Gene Name
GSK3A
Uniprot ID
P49840
Uniprot Name
Glycogen synthase kinase-3 alpha
Molecular Weight
50980.41 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Ubiquitin protein ligase binding
Specific Function
Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by pho...
Gene Name
GSK3B
Uniprot ID
P49841
Uniprot Name
Glycogen synthase kinase-3 beta
Molecular Weight
46743.865 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Receptor binding
Specific Function
Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, includ...
Gene Name
HCK
Uniprot ID
P08631
Uniprot Name
Tyrosine-protein kinase HCK
Molecular Weight
59599.355 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine-protein kinase involved in transcription regulation, p53/TP53-mediated cellular apoptosis and regulation of the cell cycle. Acts as a corepressor of several transcription factors, including SMAD1 and POU4F1/Brn3a and probably NK homeodomain transcription factors. Phosphorylates PDX1, ATF1, PML, p53/TP53, CREB1, CTBP1, CBX4, RUNX1, EP300, CTNNB1, HMGA1 and ZBTB4. Inhibits cell growth and promotes apoptosis through the activation of p53/TP53 both at the transcription level and at the protein level (by phosphorylation and indirect acetylation). The phosphorylation of p53/TP53 may be mediated by a p53/TP53-HIPK2-AXIN1 complex. Involved in the response to hypoxia by acting as a transcriptional co-suppressor of HIF1A. Mediates transcriptional activation of TP73. In response to TGFB, cooperates with DAXX to activate JNK. Negative regulator through phosphorylation and subsequent proteasomal degradation of CTNNB1 and the antiapoptotic factor CTBP1. In the Wnt/beta-catenin signaling pathway acts as an intermediate kinase between MAP3K7/TAK1 and NLK to promote the proteasomal degradation of MYB. Phosphorylates CBX4 upon DNA damage and promotes its E3 SUMO-protein ligase activity. Activates CREB1 and ATF1 transcription factors by phosphorylation in response to genotoxic stress. In response to DNA damage, stabilizes PML by phosphorylation. PML, HIPK2 and FBXO3 may act synergically to activate p53/TP53-dependent transactivation. Promotes angiogenesis, and is involved in erythroid differentiation, especially during fetal liver erythropoiesis. Phosphorylation of RUNX1 and EP300 stimulates EP300 transcription regulation activity. Triggers ZBTB4 protein degradation in response to DNA damage. Modulates HMGA1 DNA-binding affinity. In response to high glucose, triggers phosphorylation-mediated subnuclear localization shifting of PDX1. Involved in the regulation of eye size, lens formation and retinal lamination during late embryogenesis.
Specific Function
Atp binding
Gene Name
HIPK2
Uniprot ID
Q9H2X6
Uniprot Name
Homeodomain-interacting protein kinase 2
Molecular Weight
130964.705 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine-protein kinase involved in transcription regulation, apoptosis and steroidogenic gene expression. Phosphorylates JUN and RUNX2. Seems to negatively regulate apoptosis by promoting FADD phosphorylation. Enhances androgen receptor-mediated transcription. May act as a transcriptional corepressor for NK homeodomain transcription factors. The phosphorylation of NR5A1 activates SF1 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation. In osteoblasts, supports transcription activation: phosphorylates RUNX2 that synergizes with SPEN/MINT to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE).
Specific Function
Atp binding
Gene Name
HIPK3
Uniprot ID
Q9H422
Uniprot Name
Homeodomain-interacting protein kinase 3
Molecular Weight
133742.15 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Required for ciliogenesis (PubMed:24797473). Phosphorylates KIF3A (By similarity). Involved in the control of ciliary length (PubMed:24853502). Regulates the ciliary localization of SHH pathway components as well as the localization of IFT components at ciliary tips (By similarity). May play a key role in the development of multiple organ systems and particularly in cardiac development (By similarity). Regulates intraflagellar transport (IFT) speed and negatively regulates cilium length in a cAMP and mTORC1 signaling-dependent manner and this regulation requires its kinase activity (By similarity).
Specific Function
Atp binding
Gene Name
ICK
Uniprot ID
Q9UPZ9
Uniprot Name
Serine/threonine-protein kinase ICK
Molecular Weight
71426.095 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Scaffold protein binding
Specific Function
Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or oth...
Gene Name
IKBKB
Uniprot ID
O14920
Uniprot Name
Inhibitor of nuclear factor kappa-B kinase subunit beta
Molecular Weight
86563.245 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine kinase that plays an essential role in regulating inflammatory responses to viral infection, through the activation of the type I IFN, NF-kappa-B and STAT signaling. Also involved in TNFA and inflammatory cytokines, like Interleukin-1, signaling. Following activation of viral RNA sensors, such as RIG-I-like receptors, associates with DDX3X and phosphorylates interferon regulatory factors (IRFs), IRF3 and IRF7, as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the IRF3 leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNB. In order to establish such an antiviral state, IKBKE forms several different complexes whose composition depends on the type of cell and cellular stimuli. Thus, several scaffolding molecules including IPS1/MAVS, TANK, AZI2/NAP1 or TBKBP1/SINTBAD can be recruited to the IKBKE-containing-complexes. Activated by polyubiquitination in response to TNFA and interleukin-1, regulates the NF-kappa-B signaling pathway through, at least, the phosphorylation of CYLD. Phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. In addition, is also required for the induction of a subset of ISGs which displays antiviral activity, may be through the phosphorylation of STAT1 at 'Ser-708'. Phosphorylation of STAT1 at 'Ser-708' seems also to promote the assembly and DNA binding of ISGF3 (STAT1:STAT2:IRF9) complexes compared to GAF (STAT1:STAT1) complexes, in this way regulating the balance between type I and type II IFN responses. Protects cells against DNA damage-induced cell death. Also plays an important role in energy balance regulation by sustaining a state of chronic, low-grade inflammation in obesity, wich leads to a negative impact on insulin sensitivity. Phosphorylates AKT1.
Specific Function
Atp binding
Gene Name
IKBKE
Uniprot ID
Q14164
Uniprot Name
Inhibitor of nuclear factor kappa-B kinase subunit epsilon
Molecular Weight
80461.665 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Receptor signaling protein tyrosine kinase activity
Specific Function
Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (...
Gene Name
INSR
Uniprot ID
P06213
Uniprot Name
Insulin receptor
Molecular Weight
156331.465 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Receptor with tyrosine-protein kinase activity. Functions as a pH sensing receptor which is activated by increased extracellular pH. Activates an intracellular signaling pathway that involves IRS1 and AKT1/PKB.
Specific Function
Atp binding
Gene Name
INSRR
Uniprot ID
P14616
Uniprot Name
Insulin receptor-related protein
Molecular Weight
143718.73 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways. Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation. Association with MYD88 leads to IRAK1 phosphorylation by IRAK4 and subsequent autophosphorylation and kinase activation. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates the interferon regulatory factor 7 (IRF7) to induce its activation and translocation to the nucleus, resulting in transcriptional activation of type I IFN genes, which drive the cell in an antiviral state. When sumoylated, translocates to the nucleus and phosphorylates STAT3.
Specific Function
Atp binding
Gene Name
IRAK1
Uniprot ID
P51617
Uniprot Name
Interleukin-1 receptor-associated kinase 1
Molecular Weight
76535.855 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Inhibits dissociation of IRAK1 and IRAK4 from the Toll-like receptor signaling complex by either inhibiting the phosphorylation of IRAK1 and IRAK4 or stabilizing the receptor complex.
Specific Function
Atp binding
Gene Name
IRAK3
Uniprot ID
Q9Y616
Uniprot Name
Interleukin-1 receptor-associated kinase 3
Molecular Weight
67765.995 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways (PubMed:...
Gene Name
IRAK4
Uniprot ID
Q9NWZ3
Uniprot Name
Interleukin-1 receptor-associated kinase 4
Molecular Weight
51529.285 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Non-membrane spanning protein tyrosine kinase activity
Specific Function
Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-c...
Gene Name
ITK
Uniprot ID
Q08881
Uniprot Name
Tyrosine-protein kinase ITK/TSK
Molecular Weight
71830.405 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sh2 domain binding
Specific Function
Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptiv...
Gene Name
JAK2
Uniprot ID
O60674
Uniprot Name
Tyrosine-protein kinase JAK2
Molecular Weight
130672.475 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation. Mediates essential signaling events in both innate and adaptive immunity and plays a...
Gene Name
JAK3
Uniprot ID
P52333
Uniprot Name
Tyrosine-protein kinase JAK3
Molecular Weight
125097.565 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and ...
Gene Name
KDR
Uniprot ID
P35968
Uniprot Name
Vascular endothelial growth factor receptor 2
Molecular Weight
151525.555 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Not Available
Specific Function
Atp binding
Gene Name
SIK3
Uniprot ID
Q9Y2K2
Uniprot Name
Serine/threonine-protein kinase SIK3
Molecular Weight
144850.33 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell main...
Gene Name
KIT
Uniprot ID
P10721
Uniprot Name
Mast/stem cell growth factor receptor Kit
Molecular Weight
109863.655 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Negative regulator of YAP1 in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. Acts as a tumor suppressor which plays a critical role in maintenance of ploidy through its actions in both mitotic progression and the G1 tetraploidy checkpoint. Negatively regulates G2/M transition by down-regulating CDK1 kinase activity. Involved in the control of p53 expression. Affects cytokinesis by regulating actin polymerization through negative modulation of LIMK1. May also play a role in endocrine function. Plays a role in mammary gland epithelial cells differentiation, both through the Hippo signaling pathway and the intracellular estrogen receptor signaling pathway by promoting the degradation of ESR1 (PubMed:28068668).
Specific Function
Atp binding
Gene Name
LATS1
Uniprot ID
O95835
Uniprot Name
Serine/threonine-protein kinase LATS1
Molecular Weight
126868.825 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sh2 domain binding
Specific Function
Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. Plays a key role in T-ce...
Gene Name
LCK
Uniprot ID
P06239
Uniprot Name
Tyrosine-protein kinase Lck
Molecular Weight
58000.15 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Serine/threonine-protein kinase that plays an essential role in the regulation of actin filament dynamics. Acts downstream of several Rho family GTPase signal transduction pathways. Activated by up...
Gene Name
LIMK1
Uniprot ID
P53667
Uniprot Name
LIM domain kinase 1
Molecular Weight
72584.4 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Displays serine/threonine-specific phosphorylation of myelin basic protein and histone (MBP) in vitro.
Specific Function
Atp binding
Gene Name
LIMK2
Uniprot ID
P53671
Uniprot Name
LIM domain kinase 2
Molecular Weight
72231.335 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway. The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes. Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose 6 phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner. Regulates neuronal process morphology in the intact central nervous system (CNS). Plays a role in synaptic vesicle trafficking. Phosphorylates PRDX3. Has GTPase activity. May play a role in the phosphorylation of proteins central to Parkinson disease.
Specific Function
Actin binding
Gene Name
LRRK2
Uniprot ID
Q5S007
Uniprot Name
Leucine-rich repeat serine/threonine-protein kinase 2
Molecular Weight
286099.97 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Receptor with a tyrosine-protein kinase activity. The exact function of this protein is not known. Studies with chimeric proteins (replacing its extracellular region with that of several known growth factor receptors, such as EGFR and CSFIR) demonstrate its ability to promote growth and specifically neurite outgrowth, and cell survival. Signaling appears to involve the PI3 kinase pathway. Involved in regulation of the secretory pathway involving endoplasmic reticulum (ER) export sites (ERESs) and ER to Golgi transport.
Specific Function
Atp binding
Gene Name
LTK
Uniprot ID
P29376
Uniprot Name
Leukocyte tyrosine kinase receptor
Molecular Weight
91680.525 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Receptor signaling protein tyrosine kinase activity
Specific Function
Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors and plays an important role in the regulation of innate and adaptive immune responses, hematopoiesis, respons...
Gene Name
LYN
Uniprot ID
P07948
Uniprot Name
Tyrosine-protein kinase Lyn
Molecular Weight
58573.595 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Scaffold protein binding
Specific Function
Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. Activates the ERK1 and ERK2 MAP kinases (By similarity).
Gene Name
MAP2K2
Uniprot ID
P36507
Uniprot Name
Dual specificity mitogen-activated protein kinase kinase 2
Molecular Weight
44423.735 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Dual specificity kinase. Is activated by cytokines and environmental stress in vivo. Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinase p38. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14.
Specific Function
Atp binding
Gene Name
MAP2K3
Uniprot ID
P46734
Uniprot Name
Dual specificity mitogen-activated protein kinase kinase 3
Molecular Weight
39318.05 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Acts as a scaffold for the formation of a ternary MAP3K2/MAP3K3-MAP3K5-MAPK7 signaling complex. Activation of this pathway appears to play a critical role in protecting cells from stress-induced apoptosis, neuronal survival and cardiac development and angiogenesis.
Specific Function
Atp binding
Gene Name
MAP2K5
Uniprot ID
Q13163
Uniprot Name
Dual specificity mitogen-activated protein kinase kinase 5
Molecular Weight
50111.385 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. With MAP3K3/MKK3, catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinases p38 MAPK11, MAPK12, MAPK13 and MAPK14 and plays an important role in the regulation of cellular responses to cytokines and all kinds of stresses. Especially, MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the activation of MAPK11 and MAPK13 induced by environmental stress, whereas MAP2K6/MKK6 is the major MAPK11 activator in response to TNF. MAP2K6/MKK6 also phosphorylates and activates PAK6. The p38 MAP kinase signal transduction pathway leads to direct activation of transcription factors. Nuclear targets of p38 MAP kinase include the transcription factors ATF2 and ELK1. Within the p38 MAPK signal transduction pathway, MAP3K6/MKK6 mediates phosphorylation of STAT4 through MAPK14 activation, and is therefore required for STAT4 activation and STAT4-regulated gene expression in response to IL-12 stimulation. The pathway is also crucial for IL-6-induced SOCS3 expression and down-regulation of IL-6-mediated gene induction; and for IFNG-dependent gene transcription. Has a role in osteoclast differentiation through NF-kappa-B transactivation by TNFSF11, and in endochondral ossification and since SOX9 is another likely downstream target of the p38 MAPK pathway. MAP2K6/MKK6 mediates apoptotic cell death in thymocytes. Acts also as a regulator for melanocytes dendricity, through the modulation of Rho family GTPases.
Specific Function
Atp binding
Gene Name
MAP2K6
Uniprot ID
P52564
Uniprot Name
Dual specificity mitogen-activated protein kinase kinase 6
Molecular Weight
37492.055 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Component of a protein kinase signal transduction cascade. Activates the ERK and JNK kinase pathways by phosphorylation of MAP2K1 and MAP2K4. Activates CHUK and IKBKB, the central protein kinases o...
Gene Name
MAP3K1
Uniprot ID
Q13233
Uniprot Name
Mitogen-activated protein kinase kinase kinase 1
Molecular Weight
164468.265 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Activates the JUN N-terminal pathway.
Specific Function
Atp binding
Gene Name
MAP3K10
Uniprot ID
Q02779
Uniprot Name
Mitogen-activated protein kinase kinase kinase 10
Molecular Weight
103693.415 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Activates the JUN N-terminal pathway. Required for serum-stimulated cell proliferation and for mitogen and cytokine activation of MAPK14 (p38), MAPK3 (ERK) and MAPK8 (JNK1) through phosphorylation and activation of MAP2K4/MKK4 and MAP2K7/MKK7. Plays a role in mitogen-stimulated phosphorylation and activation of BRAF, but does not phosphorylate BRAF directly. Influences microtubule organization during the cell cycle.
Specific Function
Atp binding
Gene Name
MAP3K11
Uniprot ID
Q16584
Uniprot Name
Mitogen-activated protein kinase kinase kinase 11
Molecular Weight
92687.03 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
May be an activator of the JNK/SAPK pathway. Phosphorylates beta-casein, histone 1 and myelin basic protein in vitro.
Specific Function
Atp binding
Gene Name
MAP3K12
Uniprot ID
Q12852
Uniprot Name
Mitogen-activated protein kinase kinase kinase 12
Molecular Weight
93218.24 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Activates the JUN N-terminal pathway through activation of the MAP kinase kinase MAP2K7. Acts synergistically with PRDX3 to regulate the activation of NF-kappa-B in the cytosol. This activation is kinase-dependent and involves activating the IKK complex, the IKBKB-containing complex that phosphorylates inhibitors of NF-kappa-B.
Specific Function
Atp binding
Gene Name
MAP3K13
Uniprot ID
O43283
Uniprot Name
Mitogen-activated protein kinase kinase kinase 13
Molecular Weight
108295.145 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
May function in a signal transduction pathway that is activated by various cell stresses and leads to apoptosis.
Specific Function
Atp binding
Gene Name
MAP3K15
Uniprot ID
Q6ZN16
Uniprot Name
Mitogen-activated protein kinase kinase kinase 15
Molecular Weight
147435.68 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Component of a protein kinase signal transduction cascade. Regulates the JNK and ERK5 pathways by phosphorylating and activating MAP2K5 and MAP2K7 (By similarity). Plays a role in caveolae kiss-and...
Gene Name
MAP3K2
Uniprot ID
Q9Y2U5
Uniprot Name
Mitogen-activated protein kinase kinase kinase 2
Molecular Weight
69740.21 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Component of a protein kinase signal transduction cascade. Mediates activation of the NF-kappa-B, AP1 and DDIT3 transcriptional regulators.
Specific Function
Atp binding
Gene Name
MAP3K3
Uniprot ID
Q99759
Uniprot Name
Mitogen-activated protein kinase kinase kinase 3
Molecular Weight
70897.115 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Component of a protein kinase signal transduction cascade. Activates the CSBP2, P38 and JNK MAPK pathways, but not the ERK pathway. Specifically phosphorylates and activates MAP2K4 and MAP2K6.
Specific Function
Atp binding
Gene Name
MAP3K4
Uniprot ID
Q9Y6R4
Uniprot Name
Mitogen-activated protein kinase kinase kinase 4
Molecular Weight
181683.025 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Component of a protein kinase signal transduction cascade. Activates the JNK, but not ERK or p38 kinase pathways.
Specific Function
Atp binding
Gene Name
MAP3K6
Uniprot ID
O95382
Uniprot Name
Mitogen-activated protein kinase kinase kinase 6
Molecular Weight
142594.625 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the en...
Gene Name
MAP3K9
Uniprot ID
P80192
Uniprot Name
Mitogen-activated protein kinase kinase kinase 9
Molecular Weight
121893.235 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine-protein kinase, which may play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway. May play a role in hematopoietic lineage decisions and growth regulation. Able to autophosphorylate.
Specific Function
Atp binding
Gene Name
MAP4K1
Uniprot ID
Q92918
Uniprot Name
Mitogen-activated protein kinase kinase kinase kinase 1
Molecular Weight
91295.52 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine-protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Acts as a MAPK kinase kinase kinase (MAP4K) and is an upstream activator of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway and to a lesser extent of the p38 MAPKs signaling pathway. Required for the efficient activation of JNKs by TRAF6-dependent stimuli, including pathogen-associated molecular patterns (PAMPs) such as polyinosine-polycytidine (poly(IC)), lipopolysaccharides (LPS), lipid A, peptidoglycan (PGN), or bacterial flagellin. To a lesser degree, IL-1 and engagement of CD40 also stimulate MAP4K2-mediated JNKs activation. The requirement for MAP4K2/GCK is most pronounced for LPS signaling, and extends to LPS stimulation of c-Jun phosphorylation and induction of IL-8. Enhances MAP3K1 oligomerization, which may relieve N-terminal mediated MAP3K1 autoinhibition and lead to activation following autophosphorylation. Mediates also the SAP/JNK signaling pathway and the p38 MAPKs signaling pathway through activation of the MAP3Ks MAP3K10/MLK2 and MAP3K11/MLK3. May play a role in the regulation of vesicle targeting or fusion. regulation of vesicle targeting or fusion.
Specific Function
Atp binding
Gene Name
MAP4K2
Uniprot ID
Q12851
Uniprot Name
Mitogen-activated protein kinase kinase kinase kinase 2
Molecular Weight
91555.075 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
May play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway.
Specific Function
Atp binding
Gene Name
MAP4K3
Uniprot ID
Q8IVH8
Uniprot Name
Mitogen-activated protein kinase kinase kinase kinase 3
Molecular Weight
101315.145 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine kinase that may play a role in the response to environmental stress and cytokines such as TNF-alpha. Appears to act upstream of the JUN N-terminal pathway. Phosphorylates SMAD1 on Thr-322.
Specific Function
Atp binding
Gene Name
MAP4K4
Uniprot ID
O95819
Uniprot Name
Mitogen-activated protein kinase kinase kinase kinase 4
Molecular Weight
142099.84 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
May play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway.
Specific Function
Atp binding
Gene Name
MAP4K5
Uniprot ID
Q9Y4K4
Uniprot Name
Mitogen-activated protein kinase kinase kinase kinase 5
Molecular Weight
95023.135 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Map kinase kinase activity
Specific Function
Serine/threonine-protein kinase involved in various processes such as neuronal proliferation, differentiation, migration and programmed cell death. Extracellular stimuli such as proinflammatory cyt...
Gene Name
MAPK10
Uniprot ID
P53779
Uniprot Name
Mitogen-activated protein kinase 10
Molecular Weight
52585.015 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK13 is one of the four p38 MAPKs which play an important role in the cascades of cellu...
Gene Name
MAPK13
Uniprot ID
O15264
Uniprot Name
Mitogen-activated protein kinase 13
Molecular Weight
42089.28 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK14 is one of the four p38 MAPKs which play an important role in the cascades of cellu...
Gene Name
MAPK14
Uniprot ID
Q16539
Uniprot Name
Mitogen-activated protein kinase 14
Molecular Weight
41292.885 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
In vitro, phosphorylates MBP.
Specific Function
Atp binding
Gene Name
MAPK15
Uniprot ID
Q8TD08
Uniprot Name
Mitogen-activated protein kinase 15
Molecular Weight
59831.645 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Atypical MAPK protein. Phosphorylates microtubule-associated protein 2 (MAP2) and MAPKAPK5. The precise role of the complex formed with MAPKAPK5 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPKAPK5, ERK4/MAPK4 is phosphorylated at Ser-186 and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK4/MAPK4. May promote entry in the cell cycle (By similarity).
Specific Function
Atp binding
Gene Name
MAPK4
Uniprot ID
P31152
Uniprot Name
Mitogen-activated protein kinase 4
Molecular Weight
65921.01 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Plays a role in various cellular processes such as proliferation, differentiation and cell survival. The upstream activator of MAPK7 is the MAPK kinase MAP2K5. Upon activation, it translocates to the nucleus and phosphorylates various downstream targets including MEF2C. EGF activates MAPK7 through a Ras-independent and MAP2K5-dependent pathway. May have a role in muscle cell differentiation. May be important for endothelial function and maintenance of blood vessel integrity. MAP2K5 and MAPK7 interact specifically with one another and not with MEK1/ERK1 or MEK2/ERK2 pathways. Phosphorylates SGK1 at Ser-78 and this is required for growth factor-induced cell cycle progression. Involved in the regulation of p53/TP53 by disrupting the PML-MDM2 interaction.
Specific Function
Atp binding
Gene Name
MAPK7
Uniprot ID
Q13164
Uniprot Name
Mitogen-activated protein kinase 7
Molecular Weight
88385.515 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transcription factor binding
Specific Function
Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinfl...
Gene Name
MAPK9
Uniprot ID
P45984
Uniprot Name
Mitogen-activated protein kinase 9
Molecular Weight
48138.655 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Tumor suppressor serine/threonine-protein kinase involved in mTORC1 signaling and post-transcriptional regulation. Phosphorylates FOXO3, ERK3/MAPK6, ERK4/MAPK4, HSP27/HSPB1, p53/TP53 and RHEB. Acts as a tumor suppressor by mediating Ras-induced senescence and phosphorylating p53/TP53. Involved in post-transcriptional regulation of MYC by mediating phosphorylation of FOXO3: phosphorylation of FOXO3 leads to promote nuclear localization of FOXO3, enabling expression of miR-34b and miR-34c, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent MYC translation. Acts as a negative regulator of mTORC1 signaling by mediating phosphorylation and inhibition of RHEB. Part of the atypical MAPK signaling via its interaction with ERK3/MAPK6 or ERK4/MAPK4: the precise role of the complex formed with ERK3/MAPK6 or ERK4/MAPK4 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPK (ERK3/MAPK6 or ERK4/MAPK4), ERK3/MAPK6 (or ERK4/MAPK4) is phosphorylated and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK3/MAPK6 (or ERK4/MAPK4). Mediates phosphorylation of HSP27/HSPB1 in response to PKA/PRKACA stimulation, inducing F-actin rearrangement.
Specific Function
Atp binding
Gene Name
MAPKAPK5
Uniprot ID
Q8IW41
Uniprot Name
MAP kinase-activated protein kinase 5
Molecular Weight
54220.04 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine-protein kinase involved in cell polarity and microtubule dynamics regulation. Phosphorylates DCX, MAP2, MAP4 and MAPT/TAU. Involved in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3).
Specific Function
Atp binding
Gene Name
MARK1
Uniprot ID
Q9P0L2
Uniprot Name
Serine/threonine-protein kinase MARK1
Molecular Weight
89001.84 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine-protein kinase involved in cell polarity and microtubule dynamics regulation. Phosphorylates CRTC2/TORC2, DCX, HDAC7, KIF13B, MAP2, MAP4, MAPT/TAU, and RAB11FIP2. Plays a key role in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Regulates epithelial cell polarity by phosphorylating RAB11FIP2. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Regulates axogenesis by phosphorylating KIF13B, promoting interaction between KIF13B and 14-3-3 and inhibiting microtubule-dependent accumulation of KIF13B. Also required for neurite outgrowth and establishment of neuronal polarity. Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). Modulates the developmental decision to build a columnar versus a hepatic epithelial cell apparently by promoting a switch from a direct to a transcytotic mode of apical protein delivery. Essential for the asymmetric development of membrane domains of polarized epithelial cells.
Specific Function
Atp binding
Gene Name
MARK2
Uniprot ID
Q7KZI7
Uniprot Name
Serine/threonine-protein kinase MARK2
Molecular Weight
87909.995 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Involved in the specific phosphorylation of microtubule-associated proteins for tau, MAP2 and MAP4. Phosphorylates CDC25C on 'Ser-216'. Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus (PubMed:16980613). Negatively regulates the Hippo signaling pathway and antagonizes the phosphorylation of LATS1. Cooperates with DLG5 to inhibit the kinase activity of STK3/MST2 toward LATS1 (PubMed:28087714).
Specific Function
Atp binding
Gene Name
MARK3
Uniprot ID
P27448
Uniprot Name
MAP/microtubule affinity-regulating kinase 3
Molecular Weight
84427.71 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine-protein kinase (PubMed:15009667, PubMed:14594945, PubMed:23666762, PubMed:23184942). Phosphorylates the microtubule-associated protein MAPT (PubMed:14594945, PubMed:23666762). Also phosphorylates the microtubule-associated proteins MAP2 and MAP4 (PubMed:14594945). Involved in regulation of the microtubule network, causing reorganization of microtubules into bundles (PubMed:14594945, PubMed:25123532). Required for the initiation of axoneme extension during cilium assembly (PubMed:23400999). Regulates the centrosomal location of ODF2 and phosphorylates ODF2 in vitro (PubMed:23400999). Plays a role in cell cycle progression, specifically in the G1/S checkpoint (PubMed:25123532). Reduces neuronal cell survival (PubMed:15009667). Plays a role in energy homeostasis by regulating satiety and metabolic rate (By similarity). Promotes adipogenesis by activating JNK1 and inhibiting the p38MAPK pathway, and triggers apoptosis by activating the JNK1 pathway (By similarity). Phosphorylates mTORC1 complex member RPTOR and acts as a negative regulator of the mTORC1 complex, probably due to disruption of the interaction between phosphorylated RPTOR and the RRAGA/RRAGC heterodimer which is required for mTORC1 activation (PubMed:23184942).
Specific Function
Atp binding
Gene Name
MARK4
Uniprot ID
Q96L34
Uniprot Name
MAP/microtubule affinity-regulating kinase 4
Molecular Weight
82518.895 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Microtubule plus-end tracking protein that promotes the stabilization of dynamic microtubules. Involved in the nucleation of noncentrosomal microtubules originating from the trans-Golgi network (TGN). Required for the polarization of the cytoplasmic microtubule arrays in migrating cells towards the leading edge of the cell. May act at the cell cortex to enhance the frequency of rescue of depolymerizing microtubules by attaching their plus-ends to cortical platforms composed of ERC1 and PHLDB2. This cortical microtubule stabilizing activity is regulated at least in part by phosphatidylinositol 3-kinase signaling. Also performs a similar stabilizing function at the kinetochore which is essential for the bipolar alignment of chromosomes on the mitotic spindle.
Specific Function
Dystroglycan binding
Gene Name
CLASP1
Uniprot ID
Q7Z460
Uniprot Name
CLIP-associating protein 1
Molecular Weight
169448.635 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Appears to link the dystrophin/utrophin network with microtubule filaments via the syntrophins. Phosphorylation of DMD or UTRN may modulate their affinities for associated proteins (By similarity).
Specific Function
Atp binding
Gene Name
MAST1
Uniprot ID
Q9Y2H9
Uniprot Name
Microtubule-associated serine/threonine-protein kinase 1
Molecular Weight
170675.235 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Could play a significant role in the signal transduction of hematopoietic cells. May regulate tyrosine kinase activity of SRC-family members in brain by specifically phosphorylating their C-terminal regulatory tyrosine residue which acts as a negative regulatory site. It may play an inhibitory role in the control of T-cell proliferation.
Specific Function
Atp binding
Gene Name
MATK
Uniprot ID
P42679
Uniprot Name
Megakaryocyte-associated tyrosine-protein kinase
Molecular Weight
56468.51 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation. Has a broad substrate specificity; phosphorylates BCL2L14, CDC25B, MAP3K5/ASK1 and ZNF622. Acts as an activator of apoptosis by phosphorylating and activating MAP3K5/ASK1. Acts as a regulator of cell cycle, notably by mediating phosphorylation of CDC25B, promoting localization of CDC25B to the centrosome and the spindle poles during mitosis. Plays a key role in cell proliferation and carcinogenesis. Required for proliferation of embryonic and postnatal multipotent neural progenitors. Phosphorylates and inhibits BCL2L14, possibly leading to affect mammary carcinogenesis by mediating inhibition of the pro-apoptotic function of BCL2L14. Also involved in the inhibition of spliceosome assembly during mitosis by phosphorylating ZNF622, thereby contributing to its redirection to the nucleus. May also play a role in primitive hematopoiesis.
Specific Function
Atp binding
Gene Name
MELK
Uniprot ID
Q14680
Uniprot Name
Maternal embryonic leucine zipper kinase
Molecular Weight
74641.5 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6. Regulates many physiological pr...
Gene Name
MERTK
Uniprot ID
Q12866
Uniprot Name
Tyrosine-protein kinase Mer
Molecular Weight
110248.12 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine kinase which acts as a negative regulator of Ras-related Rap2-mediated signal transduction to control neuronal structure and AMPA receptor trafficking. Required for normal synaptic density, dendrite complexity, as well as surface AMPA receptor expression in hippocampal neurons. Can activate the JNK and MAPK14/p38 pathways and mediates stimulation of the stress-activated protein kinase MAPK14/p38 MAPK downstream of the Raf/ERK pathway. Phosphorylates: TANC1 upon stimulation by RAP2A, MBP and SMAD1. Has an essential function in negative selection of thymocytes, perhaps by coupling NCK1 to activation of JNK1.
Specific Function
Atp binding
Gene Name
MINK1
Uniprot ID
Q8N4C8
Uniprot Name
Misshapen-like kinase 1
Molecular Weight
149820.555 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
May play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine-containing mRNA cap.
Specific Function
Atp binding
Gene Name
MKNK1
Uniprot ID
Q9BUB5
Uniprot Name
MAP kinase-interacting serine/threonine-protein kinase 1
Molecular Weight
51341.91 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine-protein kinase that phosphorylates SFPQ/PSF, HNRNPA1 and EIF4E. May play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine-containing mRNA cap. Required for mediating PP2A-inhibition-induced EIF4E phosphorylation. Triggers EIF4E shuttling from cytoplasm to nucleus. Isoform 1 displays a high basal kinase activity, but isoform 2 exhibits a very low kinase activity. Acts as a mediator of the suppressive effects of IFNgamma on hematopoiesis. Negative regulator for signals that control generation of arsenic trioxide As(2)O(3)-dependent apoptosis and anti-leukemic responses. Involved in anti-apoptotic signaling in response to serum withdrawal.
Specific Function
Atp binding
Gene Name
MKNK2
Uniprot ID
Q9HBH9
Uniprot Name
MAP kinase-interacting serine/threonine-protein kinase 2
Molecular Weight
51874.4 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to MST1 ligand. Regulates many physiological processes including cell survival, migration and differentiation. Ligand binding at the cell surface induces autophosphorylation of RON on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1 or the adapter GAB1. Recruitment of these downstream effectors by RON leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. RON signaling activates the wound healing response by promoting epithelial cell migration, proliferation as well as survival at the wound site. Plays also a role in the innate immune response by regulating the migration and phagocytic activity of macrophages. Alternatively, RON can also promote signals such as cell migration and proliferation in response to growth factors other than MST1 ligand.
Specific Function
Atp binding
Gene Name
MST1R
Uniprot ID
Q04912
Uniprot Name
Macrophage-stimulating protein receptor
Molecular Weight
152240.095 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Receptor tyrosine kinase which plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ), the synapse between the motor neuron and the skeletal muscle (PubMed:25537362). Recruitment of AGRIN by LRP4 to the MUSK signaling complex induces phosphorylation and activation of MUSK, the kinase of the complex. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. May regulate AChR phosphorylation and clustering through activation of ABL1 and Src family kinases which in turn regulate MUSK. DVL1 and PAK1 that form a ternary complex with MUSK are also important for MUSK-dependent regulation of AChR clustering. May positively regulate Rho family GTPases through FNTA. Mediates the phosphorylation of FNTA which promotes prenylation, recruitment to membranes and activation of RAC1 a regulator of the actin cytoskeleton and of gene expression. Other effectors of the MUSK signaling include DNAJA3 which functions downstream of MUSK. May also play a role within the central nervous system by mediating cholinergic responses, synaptic plasticity and memory formation (By similarity).
Specific Function
Atp binding
Gene Name
MUSK
Uniprot ID
O15146
Uniprot Name
Muscle, skeletal receptor tyrosine-protein kinase
Molecular Weight
97055.3 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Calcium/calmodulin-dependent myosin light chain kinase implicated in smooth muscle contraction via phosphorylation of myosin light chains (MLC). Also regulates actin-myosin interaction through a non-kinase activity. Phosphorylates PTK2B/PYK2 and myosin light-chains. Involved in the inflammatory response (e.g. apoptosis, vascular permeability, leukocyte diapedesis), cell motility and morphology, airway hyperreactivity and other activities relevant to asthma. Required for tonic airway smooth muscle contraction that is necessary for physiological and asthmatic airway resistance. Necessary for gastrointestinal motility. Implicated in the regulation of endothelial as well as vascular permeability, probably via the regulation of cytoskeletal rearrangements. In the nervous system it has been shown to control the growth initiation of astrocytic processes in culture and to participate in transmitter release at synapses formed between cultured sympathetic ganglion cells. Critical participant in signaling sequences that result in fibroblast apoptosis. Plays a role in the regulation of epithelial cell survival. Required for epithelial wound healing, especially during actomyosin ring contraction during purse-string wound closure. Mediates RhoA-dependent membrane blebbing. Triggers TRPC5 channel activity in a calcium-dependent signaling, by inducing its subcellular localization at the plasma membrane. Promotes cell migration (including tumor cells) and tumor metastasis. PTK2B/PYK2 activation by phosphorylation mediates ITGB2 activation and is thus essential to trigger neutrophil transmigration during acute lung injury (ALI). May regulate optic nerve head astrocyte migration. Probably involved in mitotic cytoskeletal regulation. Regulates tight junction probably by modulating ZO-1 exchange in the perijunctional actomyosin ring. Mediates burn-induced microvascular barrier injury; triggers endothelial contraction in the development of microvascular hyperpermeability by phosphorylating MLC. Essential for intestinal barrier dysfunction. Mediates Giardia spp.-mediated reduced epithelial barrier function during giardiasis intestinal infection via reorganization of cytoskeletal F-actin and tight junctional ZO-1. Necessary for hypotonicity-induced Ca(2+) entry and subsequent activation of volume-sensitive organic osmolyte/anion channels (VSOAC) in cervical cancer cells. Responsible for high proliferative ability of breast cancer cells through anti-apoptosis.
Specific Function
Actin binding
Gene Name
MYLK
Uniprot ID
Q15746
Uniprot Name
Myosin light chain kinase, smooth muscle
Molecular Weight
210713.455 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Myosin light chain kinase activity
Specific Function
Implicated in the level of global muscle contraction and cardiac function. Phosphorylates a specific serine in the N-terminus of a myosin light chain.
Gene Name
MYLK2
Uniprot ID
Q9H1R3
Uniprot Name
Myosin light chain kinase 2, skeletal/cardiac muscle
Molecular Weight
64684.295 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Kinase that phosphorylates MYL2 in vitro. Promotes sarcomere formation in cardiomyocytes and increases cardiomyocyte contractility (By similarity).
Specific Function
Atp binding
Gene Name
MYLK3
Uniprot ID
Q32MK0
Uniprot Name
Myosin light chain kinase 3
Molecular Weight
88392.24 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Not Available
Specific Function
Atp binding
Gene Name
MYLK4
Uniprot ID
Q86YV6
Uniprot Name
Myosin light chain kinase family member 4
Molecular Weight
44507.535 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Probable actin-based motor with a protein kinase activity. Probably plays a role in vision and hearing (PubMed:12032315). Required for normal cochlear hair bundle development and hearing. Plays an important role in the early steps of cochlear hair bundle morphogenesis. Influences the number and lengths of stereocilia to be produced and limits the growth of microvilli within the forming auditory hair bundles thereby contributing to the architecture of the hair bundle, including its staircase pattern. Involved in the elongation of actin in stereocilia tips by transporting the actin regulatory factor ESPN to the plus ends of actin filaments (By similarity).
Specific Function
Actin binding
Gene Name
MYO3A
Uniprot ID
Q8NEV4
Uniprot Name
Myosin-IIIa
Molecular Weight
186206.995 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Phosphorylates serines and threonines, but also appears to possess tyrosine kinase activity (By similarity). Involved in DNA damage checkpoint control and for proper DNA damage repair. In response to injury that includes DNA damage, NEK1 phosphorylates VDAC1 to limit mitochondrial cell death (PubMed:20230784). May be implicated in the control of meiosis (By similarity). Involved in cilium assembly (PubMed:21211617).
Specific Function
14-3-3 protein binding
Gene Name
NEK1
Uniprot ID
Q96PY6
Uniprot Name
Serine/threonine-protein kinase Nek1
Molecular Weight
142827.325 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Protein kinase which plays an important role in the G2/M checkpoint response to DNA damage. Controls degradation of CDC25A by directly phosphorylating it on residues whose phosphorylation is requir...
Gene Name
NEK11
Uniprot ID
Q8NG66
Uniprot Name
Serine/threonine-protein kinase Nek11
Molecular Weight
74191.62 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Protein kinase which is involved in the control of centrosome separation and bipolar spindle formation in mitotic cells and chromatin condensation in meiotic cells. Regulates centrosome separation ...
Gene Name
NEK2
Uniprot ID
P51955
Uniprot Name
Serine/threonine-protein kinase Nek2
Molecular Weight
51762.93 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein kinase which influences neuronal morphogenesis and polarity through effects on microtubules. Regulates microtubule acetylation in neurons. Contributes to prolactin-mediated phosphorylation of PXN and VAV2. Implicated in prolactin-mediated cytoskeletal reorganization and motility of breast cancer cells through mechanisms involving RAC1 activation and phosphorylation of PXN and VAV2.
Specific Function
Atp binding
Gene Name
NEK3
Uniprot ID
P51956
Uniprot Name
Serine/threonine-protein kinase Nek3
Molecular Weight
57704.195 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein kinase that seems to act exclusively upon threonine residues (By similarity). Required for normal entry into proliferative arrest after a limited number of cell divisions, also called replicative senescence. Required for normal cell cycle arrest in response to double-stranded DNA damage.
Specific Function
Atp binding
Gene Name
NEK4
Uniprot ID
P51957
Uniprot Name
Serine/threonine-protein kinase Nek4
Molecular Weight
94596.4 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Not Available
Specific Function
Atp binding
Gene Name
NEK5
Uniprot ID
Q6P3R8
Uniprot Name
Serine/threonine-protein kinase Nek5
Molecular Weight
81444.935 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Pleiotropic regulator of mitotic progression, participating in the control of spindle dynamics and chromosome separation. Phosphorylates different histones, myelin basic protein, beta-casein, and BICD2. Phosphorylates histone H3 on serine and threonine residues and beta-casein on serine residues. Important for G1/S transition and S phase progression. Phosphorylates NEK6 and NEK7 and stimulates their activity by releasing the autoinhibitory functions of Tyr-108 and Tyr-97 respectively.
Specific Function
Atp binding
Gene Name
NEK9
Uniprot ID
Q8TD19
Uniprot Name
Serine/threonine-protein kinase Nek9
Molecular Weight
107167.69 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympatheti...
Gene Name
NTRK1
Uniprot ID
P04629
Uniprot Name
High affinity nerve growth factor receptor
Molecular Weight
87496.465 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein homodimerization activity
Specific Function
Receptor tyrosine kinase involved in the development and the maturation of the central and the peripheral nervous systems through regulation of neuron survival, proliferation, migration, differenti...
Gene Name
NTRK2
Uniprot ID
Q16620
Uniprot Name
BDNF/NT-3 growth factors receptor
Molecular Weight
91998.175 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Receptor tyrosine kinase involved in nervous system and probably heart development. Upon binding of its ligand NTF3/neurotrophin-3, NTRK3 autophosphorylates and activates different signaling pathways, including the phosphatidylinositol 3-kinase/AKT and the MAPK pathways, that control cell survival and differentiation.
Specific Function
Atp binding
Gene Name
NTRK3
Uniprot ID
Q16288
Uniprot Name
NT-3 growth factor receptor
Molecular Weight
94427.47 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine-protein kinase involved in various processes such as cell adhesion, regulation of cell ploidy and senescence, cell proliferation and tumor progression. Phosphorylates ATM, CASP6, LATS1, PPP1R12A and p53/TP53. Acts as a regulator of cellular senescence and cellular ploidy by mediating phosphorylation of 'Ser-464' of LATS1, thereby controlling its stability. Controls cell adhesion by regulating activity of the myosin protein phosphatase 1 (PP1) complex. Acts by mediating phosphorylation of PPP1R12A subunit of myosin PP1: phosphorylated PPP1R12A then interacts with 14-3-3, leading to reduced dephosphorylation of myosin MLC2 by myosin PP1. May be involved in DNA damage response: phosphorylates p53/TP53 at 'Ser-15' and 'Ser-392' and is recruited to the CDKN1A/WAF1 promoter to participate to transcription activation by p53/TP53. May also act as a tumor malignancy-associated factor by promoting tumor invasion and metastasis under regulation and phosphorylation by AKT1. Suppresses Fas-induced apoptosis by mediating phosphorylation of CASP6, thereby suppressing the activation of the caspase and the subsequent cleavage of CFLAR. Regulates UV radiation-induced DNA damage response mediated by CDKN1A. In association with STK11, phosphorylates CDKN1A in response to UV radiation and contributes to its degradation which is necessary for optimal DNA repair (PubMed:25329316).
Specific Function
Atp binding
Gene Name
NUAK1
Uniprot ID
O60285
Uniprot Name
NUAK family SNF1-like kinase 1
Molecular Weight
74304.46 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Stress-activated kinase involved in tolerance to glucose starvation. Induces cell-cell detachment by increasing F-actin conversion to G-actin. Expression is induced by CD95 or TNF-alpha, via NF-kappa-B. Protects cells from CD95-mediated apoptosis and is required for the increased motility and invasiveness of CD95-activated tumor cells. Able to phosphorylate 'Ser-464' of LATS1.
Specific Function
Atp binding
Gene Name
NUAK2
Uniprot ID
Q9H093
Uniprot Name
NUAK family SNF1-like kinase 2
Molecular Weight
69611.485 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Regulates downstream kinases in response to environmental stress. May also have a function in regulating the actin cytoskeleton.
Specific Function
Atp binding
Gene Name
OXSR1
Uniprot ID
O95747
Uniprot Name
Serine/threonine-protein kinase OSR1
Molecular Weight
58021.7 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein kinase involved in intracellular signaling pathways downstream of integrins and receptor-type kinases that plays an important role in cytoskeleton dynamics, in cell adhesion, migration, proliferation, apoptosis, mitosis, and in vesicle-mediated transport processes. Can directly phosphorylate BAD and protects cells against apoptosis. Activated by interaction with CDC42 and RAC1. Functions as GTPase effector that links the Rho-related GTPases CDC42 and RAC1 to the JNK MAP kinase pathway. Phosphorylates and activates MAP2K1, and thereby mediates activation of downstream MAP kinases. Involved in the reorganization of the actin cytoskeleton, actin stress fibers and of focal adhesion complexes. Phosphorylates the tubulin chaperone TBCB and thereby plays a role in the regulation of microtubule biogenesis and organization of the tubulin cytoskeleton. Plays a role in the regulation of insulin secretion in response to elevated glucose levels. Part of a ternary complex that contains PAK1, DVL1 and MUSK that is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ). Activity is inhibited in cells undergoing apoptosis, potentially due to binding of CDC2L1 and CDC2L2. Phosphorylates MYL9/MLC2. Phosphorylates RAF1 at 'Ser-338' and 'Ser-339' resulting in: activation of RAF1, stimulation of RAF1 translocation to mitochondria, phosphorylation of BAD by RAF1, and RAF1 binding to BCL2. Phosphorylates SNAI1 at 'Ser-246' promoting its transcriptional repressor activity by increasing its accumulation in the nucleus. In podocytes, promotes NR3C2 nuclear localization. Required for atypical chemokine receptor ACKR2-induced phosphorylation of LIMK1 and cofilin (CFL1) and for the up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3, maybe through CFL1 phosphorylation and inactivation. Plays a role in RUFY3-mediated facilitating gastric cancer cells migration and invasion (PubMed:25766321).
Specific Function
Atp binding
Gene Name
PAK1
Uniprot ID
Q13153
Uniprot Name
Serine/threonine-protein kinase PAK 1
Molecular Weight
60646.4 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell motility, cell cycle progression, apoptosis or proliferation. Acts as downstream effector of the small GTPases CDC42 and RAC1. Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Full-length PAK2 stimulates cell survival and cell growth. Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration. Phosphorylates JUN and plays an important role in EGF-induced cell proliferation. Phosphorylates many other substrates including histone H4 to promote assembly of H3.3 and H4 into nucleosomes, BAD, ribosomal protein S6, or MBP. Additionally, associates with ARHGEF7 and GIT1 to perform kinase-independent functions such as spindle orientation control during mitosis. On the other hand, apoptotic stimuli such as DNA damage lead to caspase-mediated cleavage of PAK2, generating PAK-2p34, an active p34 fragment that translocates to the nucleus and promotes cellular apoptosis involving the JNK signaling pathway. Caspase-activated PAK2 phosphorylates MKNK1 and reduces cellular translation.
Specific Function
Atp binding
Gene Name
PAK2
Uniprot ID
Q13177
Uniprot Name
Serine/threonine-protein kinase PAK 2
Molecular Weight
58042.135 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, or cell cycle regulation. Plays a role in dendrite spine morphogenesis as well as synapse formation and plasticity. Acts as downstream effector of the small GTPases CDC42 and RAC1. Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration. Additionally, phosphorylates TNNI3/troponin I to modulate calcium sensitivity and relaxation kinetics of thin myofilaments. May also be involved in early neuronal development.
Specific Function
Atp binding
Gene Name
PAK3
Uniprot ID
O75914
Uniprot Name
Serine/threonine-protein kinase PAK 3
Molecular Weight
62309.08 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, growth, proliferation or cell survival. Activation by various effectors including growth factor receptors or active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates and inactivates the protein phosphatase SSH1, leading to increased inhibitory phosphorylation of the actin binding/depolymerizing factor cofilin. Decreased cofilin activity may lead to stabilization of actin filaments. Phosphorylates LIMK1, a kinase that also inhibits the activity of cofilin. Phosphorylates integrin beta5/ITGB5 and thus regulates cell motility. Phosphorylates ARHGEF2 and activates the downstream target RHOA that plays a role in the regulation of assembly of focal adhesions and actin stress fibers. Stimulates cell survival by phosphorylating the BCL2 antagonist of cell death BAD. Alternatively, inhibits apoptosis by preventing caspase-8 binding to death domain receptors in a kinase independent manner. Plays a role in cell-cycle progression by controlling levels of the cell-cycle regulatory protein CDKN1A and by phosphorylating RAN.
Specific Function
Atp binding
Gene Name
PAK4
Uniprot ID
O96013
Uniprot Name
Serine/threonine-protein kinase PAK 4
Molecular Weight
64071.49 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine protein kinase that plays a role in the regulation of gene transcription. The kinase activity is induced by various effectors including AR or MAP2K6/MAPKK6. Phosphorylates the DNA-binding domain of androgen receptor/AR and thereby inhibits AR-mediated transcription. Inhibits also ESR1-mediated transcription. May play a role in cytoskeleton regulation by interacting with IQGAP1. May protect cells from apoptosis through phosphorylation of BAD.
Specific Function
Atp binding
Gene Name
PAK6
Uniprot ID
Q9NQU5
Uniprot Name
Serine/threonine-protein kinase PAK 6
Molecular Weight
74868.13 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, proliferation or cell survival. Activation by various effectors including growth factor receptors or active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates the proto-oncogene RAF1 and stimulates its kinase activity. Promotes cell survival by phosphorylating the BCL2 antagonist of cell death BAD. Phosphorylates CTNND1, probably to regulate cytoskeletal organization and cell morphology. Keeps microtubules stable through MARK2 inhibition and destabilizes the F-actin network leading to the disappearance of stress fibers and focal adhesions.
Specific Function
Atp binding
Gene Name
PAK5
Uniprot ID
Q9P286
Uniprot Name
Serine/threonine-protein kinase PAK 5
Molecular Weight
80744.2 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Protein kinase that plays a role in vesicle-mediated transport processes and exocytosis. Regulates GH1 release by brain neurons. Phosphorylates NSF, and thereby regulates NSF oligomerization. Requi...
Gene Name
CDK16
Uniprot ID
Q00536
Uniprot Name
Cyclin-dependent kinase 16
Molecular Weight
55715.085 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
May play a role in terminally differentiated neurons. Has a Ser/Thr-phosphorylating activity for histone H1 (By similarity).
Specific Function
Atp binding
Gene Name
CDK17
Uniprot ID
Q00537
Uniprot Name
Cyclin-dependent kinase 17
Molecular Weight
59581.69 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chem...
Gene Name
PDGFRA
Uniprot ID
P16234
Uniprot Name
Platelet-derived growth factor receptor alpha
Molecular Weight
122668.46 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Vascular endothelial growth factor binding
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic...
Gene Name
PDGFRB
Uniprot ID
P09619
Uniprot Name
Platelet-derived growth factor receptor beta
Molecular Weight
123966.895 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases. Its targets include: protein kinase B (PKB/AKT1, PKB/AKT2, PKB...
Gene Name
PDPK1
Uniprot ID
O15530
Uniprot Name
3-phosphoinositide-dependent protein kinase 1
Molecular Weight
63151.305 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Serine/threonine-protein kinase that acts like an antiapoptotic protein that counters TRAIL/TNFSF10-induced apoptosis by inducing phosphorylation of BIRC5 at 'Thr-34'.
Gene Name
CDK15
Uniprot ID
Q96Q40
Uniprot Name
Cyclin-dependent kinase 15
Molecular Weight
49022.64 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Catalytic subunit of the phosphorylase b kinase (PHK), which mediates the neural and hormonal regulation of glycogen breakdown (glycogenolysis) by phosphorylating and thereby activating glycogen phosphorylase. In vitro, phosphorylates PYGM, TNNI3, MAPT/TAU, GAP43 and NRGN/RC3 (By similarity).
Specific Function
Atp binding
Gene Name
PHKG1
Uniprot ID
Q16816
Uniprot Name
Phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform
Molecular Weight
45023.36 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Phosphorylates phosphatidylinositol (PI) in the first committed step in the production of the second messenger inositol-1,4,5,-trisphosphate (PIP). May regulate Golgi disintegration/reorganization during mitosis, possibly via its phosphorylation. Involved in Golgi-to-plasma membrane trafficking (By similarity).
Specific Function
1-phosphatidylinositol 4-kinase activity
Gene Name
PI4KB
Uniprot ID
Q9UBF8
Uniprot Name
Phosphatidylinositol 4-kinase beta
Molecular Weight
91378.045 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Phosphorylates PtdIns and PtdIns4P with a preference for PtdIns. Does not phosphorylate PtdIns(4,5)P2. May be involved in EGF and PDGF signaling cascades.
Specific Function
1-phosphatidylinositol-3-kinase activity
Gene Name
PIK3C2B
Uniprot ID
O00750
Uniprot Name
Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta
Molecular Weight
184766.065 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Generates phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) that act as second messengers. May play a role in SDF1A-stimulated chemotaxis (By similarity).
Specific Function
1-phosphatidylinositol-3-kinase activity
Gene Name
PIK3C2G
Uniprot ID
O75747
Uniprot Name
Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit gamma
Molecular Weight
165713.33 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Phosphatidylinositol-4,5-bisphosphate 3-kinase activity
Specific Function
Phosphoinositide-3-kinase (PI3K) that phosphorylates PftdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by rec...
Gene Name
PIK3CD
Uniprot ID
O00329
Uniprot Name
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
Molecular Weight
119478.065 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recr...
Gene Name
PIK3CG
Uniprot ID
P48736
Uniprot Name
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
Molecular Weight
126452.625 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transcription factor binding
Specific Function
Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis. Exerts its oncogenic activity throug...
Gene Name
PIM1
Uniprot ID
P11309
Uniprot Name
Serine/threonine-protein kinase pim-1
Molecular Weight
45411.905 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Proto-oncogene with serine/threonine kinase activity that can prevent apoptosis, promote cell survival and protein translation. May contribute to tumorigenesis through: the delivery of survival signaling through phosphorylation of BAD which induces release of the anti-apoptotic protein Bcl-X(L), the regulation of cell cycle progression, protein synthesis and by regulation of MYC transcriptional activity. Additionally to this role on tumorigenesis, can also negatively regulate insulin secretion by inhibiting the activation of MAPK1/3 (ERK1/2), through SOCS6. Involved also in the control of energy metabolism and regulation of AMPK activity in modulating MYC and PPARGC1A protein levels and cell growth.
Specific Function
Atp binding
Gene Name
PIM3
Uniprot ID
Q86V86
Uniprot Name
Serine/threonine-protein kinase pim-3
Molecular Weight
35890.755 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Participates in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.
Specific Function
1-phosphatidylinositol-3-phosphate 4-kinase activity
Gene Name
PIP4K2B
Uniprot ID
P78356
Uniprot Name
Phosphatidylinositol 5-phosphate 4-kinase type-2 beta
Molecular Weight
47377.625 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
May play an important role in the production of Phosphatidylinositol bisphosphate (PIP2), in the endoplasmic reticulum.
Specific Function
1-phosphatidylinositol-5-phosphate 4-kinase activity
Gene Name
PIP4K2C
Uniprot ID
Q8TBX8
Uniprot Name
Phosphatidylinositol 5-phosphate 4-kinase type-2 gamma
Molecular Weight
47299.52 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Acts as a negative regulator of entry into mitosis (G2 to M transition) by phosphorylation of the CDK1 kinase specifically when CDK1 is complexed to cyclins. Mediates phosphorylation of CDK1 predominantly on 'Thr-14'. Also involved in Golgi fragmentation. May be involved in phosphorylation of CDK1 on 'Tyr-15' to a lesser degree, however tyrosine kinase activity is unclear and may be indirect. May be a downstream target of Notch signaling pathway during eye development.
Specific Function
Atp binding
Gene Name
PKMYT1
Uniprot ID
Q99640
Uniprot Name
Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase
Molecular Weight
54520.78 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
PKC-related serine/threonine-protein kinase involved in various processes such as regulation of the intermediate filaments of the actin cytoskeleton, cell migration, tumor cell invasion and transcription regulation. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. Regulates the cytoskeletal network by phosphorylating proteins such as VIM and neurofilament proteins NEFH, NEFL and NEFM, leading to inhibit their polymerization. Phosphorylates 'Ser-575', 'Ser-637' and 'Ser-669' of MAPT/Tau, lowering its ability to bind to microtubules, resulting in disruption of tubulin assembly. Acts as a key coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and specifically mediating phosphorylation of 'Thr-11' of histone H3 (H3T11ph), a specific tag for epigenetic transcriptional activation that promotes demethylation of histone H3 'Lys-9' (H3K9me) by KDM4C/JMJD2C. Phosphorylates HDAC5, HDAC7 and HDAC9, leading to impair their import in the nucleus. Phosphorylates 'Thr-38' of PPP1R14A, 'Ser-159', 'Ser-163' and 'Ser-170' of MARCKS, and GFAP. Able to phosphorylate RPS6 in vitro.
Specific Function
Androgen receptor binding
Gene Name
PKN1
Uniprot ID
Q16512
Uniprot Name
Serine/threonine-protein kinase N1
Molecular Weight
103930.995 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
PKC-related serine/threonine-protein kinase and Rho/Rac effector protein that participates in specific signal transduction responses in the cell. Plays a role in the regulation of cell cycle progression, actin cytoskeleton assembly, cell migration, cell adhesion, tumor cell invasion and transcription activation signaling processes. Phosphorylates CTTN in hyaluronan-induced astrocytes and hence decreases CTTN ability to associate with filamentous actin. Phosphorylates HDAC5, therefore lead to impair HDAC5 import. Direct RhoA target required for the regulation of the maturation of primordial junctions into apical junction formation in bronchial epithelial cells. Required for G2/M phases of the cell cycle progression and abscission during cytokinesis in a ECT2-dependent manner. Stimulates FYN kinase activity that is required for establishment of skin cell-cell adhesion during keratinocytes differentiation. Regulates epithelial bladder cells speed and direction of movement during cell migration and tumor cell invasion. Inhibits Akt pro-survival-induced kinase activity. Mediates Rho protein-induced transcriptional activation via the c-fos serum response factor (SRF). Phosphorylates HCV NS5B leading to stimulation of HCV RNA replication. Involved in the negative regulation of ciliogenesis (PubMed:27104747).
Specific Function
Atp binding
Gene Name
PKN2
Uniprot ID
Q16513
Uniprot Name
Serine/threonine-protein kinase N2
Molecular Weight
112033.525 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal o...
Gene Name
PLK1
Uniprot ID
P53350
Uniprot Name
Serine/threonine-protein kinase PLK1
Molecular Weight
68254.03 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Tumor suppressor serine/threonine-protein kinase involved in synaptic plasticity, centriole duplication and G1/S phase transition. Polo-like kinases act by binding and phosphorylating proteins are that already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates CENPJ, NPM1, RAPGEF2, RASGRF1, SNCA, SIPA1L1 and SYNGAP1. Plays a key role in synaptic plasticity and memory by regulating the Ras and Rap protein signaling: required for overactivity-dependent spine remodeling by phosphorylating the Ras activator RASGRF1 and the Rap inhibitor SIPA1L1 leading to their degradation by the proteasome. Conversely, phosphorylates the Rap activator RAPGEF2 and the Ras inhibitor SYNGAP1, promoting their activity. Also regulates synaptic plasticity independently of kinase activity, via its interaction with NSF that disrupts the interaction between NSF and the GRIA2 subunit of AMPARs, leading to a rapid rundown of AMPAR-mediated current that occludes long term depression. Required for procentriole formation and centriole duplication by phosphorylating CENPJ and NPM1, respectively. Its induction by p53/TP53 suggests that it may participate in the mitotic checkpoint following stress.
Specific Function
Atp binding
Gene Name
PLK2
Uniprot ID
Q9NYY3
Uniprot Name
Serine/threonine-protein kinase PLK2
Molecular Weight
78235.87 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine-protein kinase involved in cell cycle regulation, response to stress and Golgi disassembly. Polo-like kinases act by binding and phosphorylating proteins are that already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates ATF2, BCL2L1, CDC25A, CDC25C, CHEK2, HIF1A, JUN, p53/TP53, p73/TP73, PTEN, TOP2A and VRK1. Involved in cell cycle regulation: required for entry into S phase and cytokinesis. Phosphorylates BCL2L1, leading to regulate the G2 checkpoint and progression to cytokinesis during mitosis. Plays a key role in response to stress: rapidly activated upon stress stimulation, such as ionizing radiation, reactive oxygen species (ROS), hyperosmotic stress, UV irradiation and hypoxia. Involved in DNA damage response and G1/S transition checkpoint by phosphorylating CDC25A, p53/TP53 and p73/TP73. Phosphorylates p53/TP53 in response to reactive oxygen species (ROS), thereby promoting p53/TP53-mediated apoptosis. Phosphorylates CHEK2 in response to DNA damage, promoting the G2/M transition checkpoint. Phosphorylates the transcription factor p73/TP73 in response to DNA damage, leading to inhibit p73/TP73-mediated transcriptional activation and pro-apoptotic functions. Phosphorylates HIF1A and JUN is response to hypoxia. Phosphorylates ATF2 following hyperosmotic stress in corneal epithelium. Also involved in Golgi disassembly during the cell cycle: part of a MEK1/MAP2K1-dependent pathway that induces Golgi fragmentation during mitosis by mediating phosphorylation of VRK1. May participate in endomitotic cell cycle, a form of mitosis in which both karyokinesis and cytokinesis are interrupted and is a hallmark of megakaryocyte differentiation, via its interaction with CIB1.
Specific Function
Atp binding
Gene Name
PLK3
Uniprot ID
Q9H4B4
Uniprot Name
Serine/threonine-protein kinase PLK3
Molecular Weight
71628.565 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine-protein kinase that plays a central role in centriole duplication. Able to trigger procentriole formation on the surface of the parental centriole cylinder, leading to the recruitment of centriole biogenesis proteins such as SASS6, CENPJ/CPAP, CCP110, CEP135 and gamma-tubulin. When overexpressed, it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase. Phosphorylates 'Ser-151' of FBXW5 during the G1/S transition, leading to inhibit FBXW5 ability to ubiquitinate SASS6. Its central role in centriole replication suggests a possible role in tumorigenesis, centrosome aberrations being frequently observed in tumors. Also involved in deuterosome-mediated centriole amplification in multiciliated that can generate more than 100 centrioles. Also involved in trophoblast differentiation by phosphorylating HAND1, leading to disrupt the interaction between HAND1 and MDFIC and activate HAND1. Phosphorylates CDC25C and CHEK2. Required for the recruitment of STIL to the centriole and for STIL-mediated centriole amplification (PubMed:22020124).
Specific Function
Atp binding
Gene Name
PLK4
Uniprot ID
O00444
Uniprot Name
Serine/threonine-protein kinase PLK4
Molecular Weight
108971.055 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Tau-protein kinase activity
Specific Function
Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular A...
Gene Name
PRKAA1
Uniprot ID
Q13131
Uniprot Name
5'-AMP-activated protein kinase catalytic subunit alpha-1
Molecular Weight
64008.64 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Tau-protein kinase activity
Specific Function
Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular A...
Gene Name
PRKAA1
Uniprot ID
Q13131
Uniprot Name
5'-AMP-activated protein kinase catalytic subunit alpha-1
Molecular Weight
64008.64 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Ubiquitin protein ligase binding
Specific Function
Mediates cAMP-dependent signaling triggered by receptor binding to GPCRs. PKA activation regulates diverse cellular processes such as cell proliferation, the cell cycle, differentiation and regulat...
Gene Name
PRKACB
Uniprot ID
P22694
Uniprot Name
cAMP-dependent protein kinase catalytic subunit beta
Molecular Weight
40622.39 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic ...
Gene Name
PRKCD
Uniprot ID
Q05655
Uniprot Name
Protein kinase C delta type
Molecular Weight
77504.445 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Signal transducer activity
Specific Function
Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays essential roles in the regulation of multiple cellular processes linked to cytoskele...
Gene Name
PRKCE
Uniprot ID
Q02156
Uniprot Name
Protein kinase C epsilon type
Molecular Weight
83673.2 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays diverse roles in neuronal cells and eye tissues, such as regulation of the neuronal receptors GRIA4/GLUR4 and GRIN1/NMDAR1, modulation of receptors and neuronal functions related to sensitivity to opiates, pain and alcohol, mediation of synaptic function and cell survival after ischemia, and inhibition of gap junction activity after oxidative stress. Binds and phosphorylates GRIA4/GLUR4 glutamate receptor and regulates its function by increasing plasma membrane-associated GRIA4 expression. In primary cerebellar neurons treated with the agonist 3,5-dihyidroxyphenylglycine, functions downstream of the metabotropic glutamate receptor GRM5/MGLUR5 and phosphorylates GRIN1/NMDAR1 receptor which plays a key role in synaptic plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning. May be involved in the regulation of hippocampal long-term potentiation (LTP), but may be not necessary for the process of synaptic plasticity. May be involved in desensitization of mu-type opioid receptor-mediated G-protein activation in the spinal cord, and may be critical for the development and/or maintenance of morphine-induced reinforcing effects in the limbic forebrain. May modulate the functionality of mu-type-opioid receptors by participating in a signaling pathway which leads to the phosphorylation and degradation of opioid receptors. May also contributes to chronic morphine-induced changes in nociceptive processing. Plays a role in neuropathic pain mechanisms and contributes to the maintenance of the allodynia pain produced by peripheral inflammation. Plays an important role in initial sensitivity and tolerance to ethanol, by mediating the behavioral effects of ethanol as well as the effects of this drug on the GABA(A) receptors. During and after cerebral ischemia modulate neurotransmission and cell survival in synaptic membranes, and is involved in insulin-induced inhibition of necrosis, an important mechanism for minimizing ischemic injury. Required for the elimination of multiple climbing fibers during innervation of Purkinje cells in developing cerebellum. Is activated in lens epithelial cells upon hydrogen peroxide treatment, and phosphorylates connexin-43 (GJA1/CX43), resulting in disassembly of GJA1 gap junction plaques and inhibition of gap junction activity which could provide a protective effect against oxidative stress (By similarity). Phosphorylates p53/TP53 and promotes p53/TP53-dependent apoptosis in response to DNA damage. Involved in the phase resetting of the cerebral cortex circadian clock during temporally restricted feeding. Stabilizes the core clock component ARNTL/BMAL1 by interfering with its ubiquitination, thus suppressing its degradation, resulting in phase resetting of the cerebral cortex clock (By similarity).
Specific Function
Atp binding
Gene Name
PRKCG
Uniprot ID
P05129
Uniprot Name
Protein kinase C gamma type
Molecular Weight
78447.23 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Calcium- and diacylglycerol-independent serine/ threonine-protein kinase that plays a general protective role against apoptotic stimuli, is involved in NF-kappa-B activation, cell survival, differe...
Gene Name
PRKCI
Uniprot ID
P41743
Uniprot Name
Protein kinase C iota type
Molecular Weight
68261.855 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Ubiquitin-protein transferase activity
Specific Function
Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that mediates non-redundant functions in T-cell receptor (TCR) signaling, including T-cells act...
Gene Name
PRKCQ
Uniprot ID
Q04759
Uniprot Name
Protein kinase C theta type
Molecular Weight
81864.145 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and trafficking, cell survival through NF-kappa-B activation, cell migration, cell differentiation by mediating HDAC7 nuclear export, cell proliferation via MAPK1/3 (ERK1/2) signaling, and plays a role in cardiac hypertrophy, VEGFA-induced angiogenesis, genotoxic-induced apoptosis and flagellin-stimulated inflammatory response. Phosphorylates the epidermal growth factor receptor (EGFR) on dual threonine residues, which leads to the suppression of epidermal growth factor (EGF)-induced MAPK8/JNK1 activation and subsequent JUN phosphorylation. Phosphorylates RIN1, inducing RIN1 binding to 14-3-3 proteins YWHAB, YWHAE and YWHAZ and increased competition with RAF1 for binding to GTP-bound form of Ras proteins (NRAS, HRAS and KRAS). Acts downstream of the heterotrimeric G-protein beta/gamma-subunit complex to maintain the structural integrity of the Golgi membranes, and is required for protein transport along the secretory pathway. In the trans-Golgi network (TGN), regulates the fission of transport vesicles that are on their way to the plasma membrane. May act by activating the lipid kinase phosphatidylinositol 4-kinase beta (PI4KB) at the TGN for the local synthesis of phosphorylated inositol lipids, which induces a sequential production of DAG, phosphatidic acid (PA) and lyso-PA (LPA) that are necessary for membrane fission and generation of specific transport carriers to the cell surface. Under oxidative stress, is phosphorylated at Tyr-463 via SRC-ABL1 and contributes to cell survival by activating IKK complex and subsequent nuclear translocation and activation of NFKB1. Involved in cell migration by regulating integrin alpha-5/beta-3 recycling and promoting its recruitment in newly forming focal adhesion. In osteoblast differentiation, mediates the bone morphogenetic protein 2 (BMP2)-induced nuclear export of HDAC7, which results in the inhibition of HDAC7 transcriptional repression of RUNX2. In neurons, plays an important role in neuronal polarity by regulating the biogenesis of TGN-derived dendritic vesicles, and is involved in the maintenance of dendritic arborization and Golgi structure in hippocampal cells. May potentiate mitogenesis induced by the neuropeptide bombesin or vasopressin by mediating an increase in the duration of MAPK1/3 (ERK1/2) signaling, which leads to accumulation of immediate-early gene products including FOS that stimulate cell cycle progression. Plays an important role in the proliferative response induced by low calcium in keratinocytes, through sustained activation of MAPK1/3 (ERK1/2) pathway. Downstream of novel PKC signaling, plays a role in cardiac hypertrophy by phosphorylating HDAC5, which in turn triggers XPO1/CRM1-dependent nuclear export of HDAC5, MEF2A transcriptional activation and induction of downstream target genes that promote myocyte hypertrophy and pathological cardiac remodeling. Mediates cardiac troponin I (TNNI3) phosphorylation at the PKA sites, which results in reduced myofilament calcium sensitivity, and accelerated crossbridge cycling kinetics. The PRKD1-HDAC5 pathway is also involved in angiogenesis by mediating VEGFA-induced specific subset of gene expression, cell migration, and tube formation. In response to VEGFA, is necessary and required for HDAC7 phosphorylation which induces HDAC7 nuclear export and endothelial cell proliferation and migration. During apoptosis induced by cytarabine and other genotoxic agents, PRKD1 is cleaved by caspase-3 at Asp-378, resulting in activation of its kinase function and increased sensitivity of cells to the cytotoxic effects of genotoxic agents. In epithelial cells, is required for transducing flagellin-stimulated inflammatory responses by binding and phosphorylating TLR5, which contributes to MAPK14/p38 activation and production of inflammatory cytokines. May play a role in inflammatory response by mediating activation of NF-kappa-B. May be involved in pain transmission by directly modulating TRPV1 receptor. Plays a role in activated KRAS-mediated stabilization of ZNF304 in colorectal cancer (CRC) cells (PubMed:24623306). Regulates nuclear translocation of transcription factor TFEB in macrophages upon live S.enterica infection (By similarity).
Specific Function
Atp binding
Gene Name
PRKD1
Uniprot ID
Q15139
Uniprot Name
Serine/threonine-protein kinase D1
Molecular Weight
101703.275 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Crucial regulator of intestinal secretion and bone growth (By similarity). Phosphorylates and activates CFTR on the plasma membrane. Plays a key role in intestinal secretion by regulating cGMP-dependent translocation of CFTR in jejunum (By similarity). Acts downstream of NMDAR to activate the plasma membrane accumulation of GRIA1/GLUR1 in synapse and increase synaptic plasticity. Phosphorylates GRIA1/GLUR1 at Ser-863 (By similarity). Acts as regulator of gene expression and activator of the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2 in mechanically stimulated osteoblasts. Under fluid shear stress, mediates ERK activation and subsequent induction of FOS, FOSL1/FRA1, FOSL2/FRA2 and FOSB that play a key role in the osteoblast anabolic response to mechanical stimulation (By similarity).
Specific Function
Atp binding
Gene Name
PRKG2
Uniprot ID
Q13237
Uniprot Name
cGMP-dependent protein kinase 2
Molecular Weight
87431.475 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Has a role in pre-mRNA splicing. Phosphorylates SF2/ASF.
Specific Function
Atp binding
Gene Name
PRPF4B
Uniprot ID
Q13523
Uniprot Name
Serine/threonine-protein kinase PRP4 homolog
Molecular Weight
116985.72 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Signal transducer activity
Specific Function
Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adh...
Gene Name
PTK2
Uniprot ID
Q05397
Uniprot Name
Focal adhesion kinase 1
Molecular Weight
119232.025 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Signal transducer activity
Specific Function
Non-receptor protein-tyrosine kinase that regulates reorganization of the actin cytoskeleton, cell polarization, cell migration, adhesion, spreading and bone remodeling. Plays a role in the regulat...
Gene Name
PTK2B
Uniprot ID
Q14289
Uniprot Name
Protein-tyrosine kinase 2-beta
Molecular Weight
115873.62 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Receptor binding
Specific Function
Non-receptor tyrosine-protein kinase implicated in the regulation of a variety of signaling pathways that control the differentiation and maintenance of normal epithelia, as well as tumor growth. F...
Gene Name
PTK6
Uniprot ID
Q13882
Uniprot Name
Protein-tyrosine kinase 6
Molecular Weight
51833.72 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determin...
Gene Name
RAF1
Uniprot ID
P04049
Uniprot Name
RAF proto-oncogene serine/threonine-protein kinase
Molecular Weight
73051.025 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell de...
Gene Name
RET
Uniprot ID
P07949
Uniprot Name
Proto-oncogene tyrosine-protein kinase receptor Ret
Molecular Weight
124317.465 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Involved in the final steps of cytoplasmic maturation of the 40S ribosomal subunit. Involved in processing of 18S-E pre-rRNA to the mature 18S rRNA. Required for the recycling of NOB1 and PNO1 from the late 40S precursor (PubMed:22072790). The association with the very late 40S subunit intermediate may involve a translation-like checkpoint point cycle preceeding the binding to the 60S ribosomal subunit (By similarity). Despite the protein kinase domain is proposed to act predominantly as an ATPase (By similarity). The catalytic activity regulates its dynamic association with the 40S subunit (By similarity).
Specific Function
Atp binding
Gene Name
RIOK1
Uniprot ID
Q9BRS2
Uniprot Name
Serine/threonine-protein kinase RIO1
Molecular Weight
65582.485 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine-protein kinase involved in the final steps of cytoplasmic maturation of the 40S ribosomal subunit. Involved in export of the 40S pre-ribosome particles (pre-40S) from the nucleus to the cytoplasm. Its kinase activity is required for the release of NOB1, PNO1 and LTV1 from the late pre-40S and the processing of 18S-E pre-rRNA to the mature 18S rRNA (PubMed:19564402). Regulates the timing of the metaphase-anaphase transition during mitotic progression, and its phosphorylation, most likely by PLK1, regulates this function (PubMed:21880710).
Specific Function
Atp binding
Gene Name
RIOK2
Uniprot ID
Q9BVS4
Uniprot Name
Serine/threonine-protein kinase RIO2
Molecular Weight
63282.565 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Involved in regulation of type I interferon (IFN)-dependent immune response which plays a critical role in the innate immune response against DNA and RNA viruses. May act as an adapter protein essential for the recruitment of TBK1 to IRF3 (PubMed:24807708). Phosphorylates IFIH1 on 'Ser-828' interfering with IFIH1 filament assembly on long dsRNA and resulting in attenuated IFIH1-signaling (PubMed:25865883). Can inhibit CASP10 isoform 7-mediated activation of the NF-kappaB signaling pathway (PubMed:19557502). May play a role in the biogenesis of the 40S ribosomal subunit. Involved in the processing of 21S pre-rRNA to the mature 18S rRNA (PubMed:22418843).
Specific Function
Atp binding
Gene Name
RIOK3
Uniprot ID
O14730
Uniprot Name
Serine/threonine-protein kinase RIO3
Molecular Weight
59092.58 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine-threonine kinase which transduces inflammatory and cell-death signals (programmed necrosis) following death receptors ligation, activation of pathogen recognition receptors (PRRs), and DNA damage. Upon activation of TNFR1 by the TNF-alpha family cytokines, TRADD and TRAF2 are recruited to the receptor. Phosphorylates DAB2IP at 'Ser-728' in a TNF-alpha-dependent manner, and thereby activates the MAP3K5-JNK apoptotic cascade. Ubiquitination by TRAF2 via 'Lys-63'-link chains acts as a critical enhancer of communication with downstream signal transducers in the mitogen-activated protein kinase pathway and the NF-kappa-B pathway, which in turn mediate downstream events including the activation of genes encoding inflammatory molecules. Polyubiquitinated protein binds to IKBKG/NEMO, the regulatory subunit of the IKK complex, a critical event for NF-kappa-B activation. Interaction with other cellular RHIM-containing adapters initiates gene activation and cell death. RIPK1 and RIPK3 association, in particular, forms a necrosis-inducing complex.
Specific Function
Atp binding
Gene Name
RIPK1
Uniprot ID
Q13546
Uniprot Name
Receptor-interacting serine/threonine-protein kinase 1
Molecular Weight
75930.35 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine/tyrosine kinase that plays an essential role in modulation of innate and adaptive immune responses. Upon stimulation by bacterial peptidoglycans, NOD1 and NOD2 are activated, oligomerize and recruit RIPK2 through CARD-CARD domains. Contributes to the tyrosine phosphorylation of the guanine exchange factor ARHGEF2 through Src tyrosine kinase leading to NF-kappaB activation by NOD2. Once recruited, RIPK2 autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases XIAP, BIRC2 and BIRC3. The polyubiquitinated protein mediates the recruitment of MAP3K7/TAK1 to IKBKG/NEMO and induces 'Lys-63'-linked polyubiquitination of IKBKG/NEMO and subsequent activation of IKBKB/IKKB. In turn, NF-kappa-B is released from NF-kappa-B inhibitors and translocates into the nucleus where it activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. Plays also a role during engagement of the T-cell receptor (TCR) in promoting BCL10 phosphorylation and subsequent NF-kappa-B activation.
Specific Function
Atp binding
Gene Name
RIPK2
Uniprot ID
O43353
Uniprot Name
Receptor-interacting serine/threonine-protein kinase 2
Molecular Weight
61194.345 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Involved in stratified epithelial development. It is a direct transcriptional target of TP63. Plays a role in NF-kappa-B activation.
Specific Function
Atp binding
Gene Name
RIPK4
Uniprot ID
P57078
Uniprot Name
Receptor-interacting serine/threonine-protein kinase 4
Molecular Weight
91609.925 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Structural molecule activity
Specific Function
Protein kinase which is a key regulator of actin cytoskeleton and cell polarity. Involved in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesio...
Gene Name
ROCK2
Uniprot ID
O75116
Uniprot Name
Rho-associated protein kinase 2
Molecular Weight
160898.555 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Orphan receptor tyrosine kinase (RTK) that plays a role in epithelial cell differentiation and regionalization of the proximal epididymal epithelium. May activate several downstream signaling pathways related to cell differentiation, proliferation, growth and survival including the PI3 kinase-mTOR signaling pathway. Mediates the phosphorylation of PTPN11, an activator of this pathway. May also phosphorylate and activate the transcription factor STAT3 to control anchorage-independent cell growth. Mediates the phosphorylation and the activation of VAV3, a guanine nucleotide exchange factor regulating cell morphology. May activate other downstream signaling proteins including AKT1, MAPK1, MAPK3, IRS1 and PLCG2.
Specific Function
Atp binding
Gene Name
ROS1
Uniprot ID
P08922
Uniprot Name
Proto-oncogene tyrosine-protein kinase ROS
Molecular Weight
263912.88 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Ribosomal protein s6 kinase activity
Specific Function
Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 ...
Gene Name
RPS6KA1
Uniprot ID
Q15418
Uniprot Name
Ribosomal protein S6 kinase alpha-1
Molecular Weight
82722.36 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Ribosomal protein s6 kinase activity
Specific Function
Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 ...
Gene Name
RPS6KA3
Uniprot ID
P51812
Uniprot Name
Ribosomal protein S6 kinase alpha-3
Molecular Weight
83735.325 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
May be involved in signal-transduction pathways related to the control of brain development.
Specific Function
Atp binding
Gene Name
SBK1
Uniprot ID
Q52WX2
Uniprot Name
Serine/threonine-protein kinase SBK1
Molecular Weight
46251.265 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Not Available
Specific Function
Atp binding
Gene Name
SBK3
Uniprot ID
P0C264
Uniprot Name
Uncharacterized serine/threonine-protein kinase SBK3
Molecular Weight
38487.27 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine-protein kinase which is involved in the regulation of a wide variety of ion channels, membrane transporters, cell growth, proliferation, survival and migration. Up-regulates Na(+) channels: SCNN1A/ENAC and SCN5A, K(+) channels: KCNA3/KV1.3, KCNE1, KCNQ1 and KCNH2/HERG, epithelial Ca(2+) channels: TRPV5 and TRPV6, chloride channel: BSND, creatine transporter: SLC6A8, Na(+)/dicarboxylate cotransporter: SLC13A2/NADC1, Na(+)-dependent phosphate cotransporter: SLC34A2/NAPI-2B, amino acid transporters: SLC1A5/ASCT2 and SLC6A19, glutamate transporters: SLC1A3/EAAT1, SLC1A6/EAAT4 and SLC1A7/EAAT5, glutamate receptors: GRIA1/GLUR1 and GRIK2/GLUR6, Na(+)/H(+) exchanger: SLC9A3/NHE3, and the Na(+)/K(+) ATPase. Plays a role in the regulation of renal tubular phosphate transport and bone density. Phosphorylates NEDD4L and GSK3B. Positively regulates ER transcription activity through phosphorylation of FLII. Negatively regulates the function of ITCH/AIP4 via its phosphorylation and thereby prevents CXCR4 from being efficiently sorted to lysosomes.
Specific Function
Atp binding
Gene Name
SGK3
Uniprot ID
Q96BR1
Uniprot Name
Serine/threonine-protein kinase Sgk3
Molecular Weight
57107.655 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, gluconeogenesis and lipogenesis regulation, muscle growth and differentiation and tumor suppression. Pho...
Gene Name
SIK1
Uniprot ID
P57059
Uniprot Name
Serine/threonine-protein kinase SIK1
Molecular Weight
84901.25 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Phosphorylates 'Ser-794' of IRS1 in insulin-stimulated adipocytes, potentially modulating the efficiency of insulin signal transduction. Inhibits CREB activity by phosphorylating and repressing TORCs, the CREB-specific coactivators.
Specific Function
Atp binding
Gene Name
SIK2
Uniprot ID
Q9H0K1
Uniprot Name
Serine/threonine-protein kinase SIK2
Molecular Weight
103914.445 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Mediates apoptosis and actin stress fiber dissolution.
Gene Name
SLK
Uniprot ID
Q9H2G2
Uniprot Name
STE20-like serine/threonine-protein kinase
Molecular Weight
142693.96 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
May play a role in hematopoietic cell proliferation or differentiation. Potential mediator of neuronal apoptosis.
Specific Function
Atp binding
Gene Name
SNRK
Uniprot ID
Q9NRH2
Uniprot Name
SNF-related serine/threonine-protein kinase
Molecular Weight
84275.47 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sh3/sh2 adaptor activity
Specific Function
Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion recept...
Gene Name
SRC
Uniprot ID
P12931
Uniprot Name
Proto-oncogene tyrosine-protein kinase Src
Molecular Weight
59834.295 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Non-receptor tyrosine-protein kinase which phosphorylates DOK1 on tyrosine residues. May be involved in proliferation or differentiation of keratinocytes in the skin.
Specific Function
Atp binding
Gene Name
SRMS
Uniprot ID
Q9H3Y6
Uniprot Name
Tyrosine-protein kinase Srms
Molecular Weight
54506.255 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine/threonine-protein kinase involved in regulation of lymphocyte migration. Phosphorylates MSN, and possibly PLK1. Involved in regulation of lymphocyte migration by mediating phosphorylation of ERM proteins such as MSN. Acts as a negative regulator of MAP3K1/MEKK1. May also act as a cell cycle regulator by acting as a polo kinase kinase: mediates phosphorylation of PLK1 in vitro; however such data require additional evidences in vivo.
Specific Function
Atp binding
Gene Name
STK10
Uniprot ID
O94804
Uniprot Name
Serine/threonine-protein kinase 10
Molecular Weight
112134.415 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Membrane-associated protein kinase that phosphorylates on serine and threonine residues. In vitro substrates include DRG1, ENO1 and EIF4EBP1. Also autophosphorylates. May be involved in secretory vesicle trafficking or intracellular signaling. May have a role in regulating stromal-epithelial interactions that occur during ductal morphogenesis in the mammary gland. May be involved in TGF-beta signaling. Able to autophosphorylate on Tyr residue; it is however unclear whether it has tyrosine-protein kinase toward other proteins.
Specific Function
Atp binding
Gene Name
STK16
Uniprot ID
O75716
Uniprot Name
Serine/threonine-protein kinase 16
Molecular Weight
34655.63 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Acts as a positive regulator of apoptosis. Also acts as a regulator of cellular reactive oxygen species.
Specific Function
Atp binding
Gene Name
STK17A
Uniprot ID
Q9UEE5
Uniprot Name
Serine/threonine-protein kinase 17A
Molecular Weight
46557.745 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Phosphorylates myosin light chains (By similarity). Acts as a positive regulator of apoptosis.
Gene Name
STK17B
Uniprot ID
O94768
Uniprot Name
Serine/threonine-protein kinase 17B
Molecular Weight
42343.595 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Not Available
Specific Function
Atp binding
Gene Name
STK32A
Uniprot ID
Q8WU08
Uniprot Name
Serine/threonine-protein kinase 32A
Molecular Weight
46368.895 Da
References
  1. Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M: In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. [PubMed:26516587]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks trans...
Gene Name
UGT1A9
Uniprot ID
O60656
Uniprot Name
UDP-glucuronosyltransferase 1-9
Molecular Weight
59940.495 Da

Transporters

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Efflux transmembrane transporter activity
Specific Function
Drug efflux transporter present in a number of stem cells that acts as a regulator of cellular differentiation. Able to mediate efflux from cells of the rhodamine dye and of the therapeutic drug do...
Gene Name
ABCB5
Uniprot ID
Q2M3G0
Uniprot Name
ATP-binding cassette sub-family B member 5
Molecular Weight
138639.48 Da

Drug created on October 20, 2016 15:10 / Updated on November 02, 2018 09:14