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Identification
NameBosutinib
Accession NumberDB06616
TypeSmall Molecule
GroupsApproved
Description

Bosutinib is a Bcr-Abl kinase inhibitor for the treatment of Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML). Compared to other tyrosine kinase inhibitors, it has a more favourable hematologic toxicity profile. FDA approved on September 4, 2012.

Structure
Thumb
Synonyms
4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methyl-1-piperazinyl)propoxy)-3-quinolinecarbonitrile
Bosulif®
Bosutinib
Bosutinib Monohydrate
SKI 606
SKI-606
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Bosuliftablet, film coated100 mg/1oralPfizer Laboratories Div Pfizer Inc2012-09-04Not applicableUs
Bosuliftablet500 mgoralPfizer Canada Inc2014-03-24Not applicableCanada
Bosuliftablet100 mgoralPfizer Canada Inc2014-04-24Not applicableCanada
Bosuliftablet, film coated100 mg/1oralU.S. Pharmaceuticals2012-09-04Not applicableUs
Bosuliftablet, film coated500 mg/1oralPfizer Laboratories Div Pfizer Inc2012-09-04Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII5018V4AEZ0
CAS number380843-75-4
WeightAverage: 530.446
Monoisotopic: 529.164745233
Chemical FormulaC26H29Cl2N5O3
InChI KeyInChIKey=UBPYILGKFZZVDX-UHFFFAOYSA-N
InChI
InChI=1S/C26H29Cl2N5O3/c1-32-6-8-33(9-7-32)5-4-10-36-25-13-21-18(11-24(25)35-3)26(17(15-29)16-30-21)31-22-14-23(34-2)20(28)12-19(22)27/h11-14,16H,4-10H2,1-3H3,(H,30,31)
IUPAC Name
4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-3-carbonitrile
SMILES
COC1=CC(NC2=C(C=NC3=CC(OCCCN4CCN(C)CC4)=C(OC)C=C23)C#N)=C(Cl)C=C1Cl
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as aminoquinolines and derivatives. These are organic compounds containing an amino group attached to a quinoline ring system.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassQuinolines and derivatives
Sub ClassAminoquinolines and derivatives
Direct ParentAminoquinolines and derivatives
Alternative Parents
Substituents
  • Hydroxyquinoline
  • Aminoquinoline
  • Methoxyaniline
  • Methoxybenzene
  • Substituted aniline
  • Phenol ether
  • 1,3-dichlorobenzene
  • Anisole
  • N-alkylpiperazine
  • N-methylpiperazine
  • Halobenzene
  • Chlorobenzene
  • Aniline
  • Aminopyridine
  • Alkyl aryl ether
  • Benzenoid
  • Pyridine
  • Piperazine
  • 1,4-diazinane
  • Monocyclic benzene moiety
  • Aryl halide
  • Aryl chloride
  • Heteroaromatic compound
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Secondary amine
  • Nitrile
  • Carbonitrile
  • Ether
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationTreatment of chronic, accelerated, or blast phase Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) with resistance or intolerance to prior therapy in adult patients.
PharmacodynamicsNot Available
Mechanism of actionBosutinib is a tyrosine kinase inhibitor. Although it is able to inhibit several tyrosine kinases such as Src, Lyn, and Hck, which are members of the Src-family of kinases, its primary target is the Bcr-Abl kinase. The Bcr-Abl gene is a chimeric oncogene created from the fusion of the breakpoint-cluster (Bcr) gene and Abelson (Abl) tyrosine gene. This chromosomal abnormality results in the formation of what is commonly known as the Philadelphia chromosome or Philadelphia translocation. The Bcr-Abl gene expresses a particular kinase that promotes the progression of CML. A decrease in the growth and size of the CML tumour has been observed following administration of bosutinib. Bosutinib did not inhibit the T315I and V299L mutant cells.
Related Articles
AbsorptionFood increase the exposure of bosutinib. Tmax, single dose, cancer patients, fed-state = 4-6 hours; After 15 daily doses of bosutinib 500 mg with food in CML patients, the pharmacokinetic parameters are as follows: Cmax = 200 ng/mL; AUC = 3650 ng∙h/mL
Volume of distribution

Apparent volume of distribution = 6080 ± 1230 L.

Protein binding94% bound to human plasma proteins in vitro. 96% bound to human plasma proteins in healthy subjects ex vivo. Extent of protein binding is not concentration-dependent.
Metabolism

Bosutinib is primarily metabolized by CYP3A4. The major circulating metabolites identified in plasma are oxydechlorinated (M2) bosutinib (19% of parent exposure) and N-desmethylated (M5) bosutinib (25% of parent exposure), with bosutinib N-oxide (M6) as a minor circulating metabolite. All the metabolites were deemed inactive.

Route of eliminationWhen given a single oral dose, 91.3% of the dose was recovered in feces and 3% of the dose recovered in urine.
Half lifeTerminal phase elimination half-life, single oral dose, fed-state = 22.5 hours
Clearance

Mean clearance (CL/F), single oral dose, fed-state = 189 L/h

ToxicityMost common adverse reactions (incidence greater than 20%) are diarrhea, nausea, thrombocytopenia, vomiting, abdominal pain, rash, anemia, pyrexia, and fatigue. Because bosutinib is not an inhibitor of c-KIT or PDGF receptor, it has less hematologic toxicities.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9823
Blood Brain Barrier+0.9272
Caco-2 permeable+0.6542
P-glycoprotein substrateSubstrate0.7601
P-glycoprotein inhibitor IInhibitor0.8409
P-glycoprotein inhibitor IIInhibitor0.9108
Renal organic cation transporterInhibitor0.5663
CYP450 2C9 substrateNon-substrate0.854
CYP450 2D6 substrateNon-substrate0.6953
CYP450 3A4 substrateSubstrate0.6987
CYP450 1A2 substrateInhibitor0.5606
CYP450 2C9 inhibitorNon-inhibitor0.7372
CYP450 2D6 inhibitorNon-inhibitor0.5136
CYP450 2C19 inhibitorNon-inhibitor0.5725
CYP450 3A4 inhibitorInhibitor0.5
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7021
Ames testAMES toxic0.5922
CarcinogenicityNon-carcinogens0.8869
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.4201 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.6147
hERG inhibition (predictor II)Inhibitor0.7754
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Tabletoral100 mg
Tabletoral500 mg
Tablet, film coatedoral100 mg/1
Tablet, film coatedoral500 mg/1
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6002008 No1998-03-272018-03-27Us
US7417148 No2006-01-232026-01-23Us
US7767678 No2006-11-232026-11-23Us
US7919625 No2005-12-112025-12-11Us
USRE42376 No1999-09-242019-09-24Us
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0095 mg/mLALOGPS
logP4.87ALOGPS
logP4.09ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)15.48ChemAxon
pKa (Strongest Basic)8.43ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area82.88 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity142.12 m3·mol-1ChemAxon
Polarizability56.14 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. Amsberg GK, Schafhausen P: Bosutinib in the management of chronic myelogenous leukemia. Biologics. 2013;7:115-22. doi: 10.2147/BTT.S30182. Epub 2013 May 6. [PubMed:23674887 ]
  2. Keller-V Amsberg G, Brummendorf TH: Novel aspects of therapy with the dual Src and Abl kinase inhibitor bosutinib in chronic myeloid leukemia. Expert Rev Anticancer Ther. 2012 Sep;12(9):1121-7. doi: 10.1586/era.12.84. [PubMed:23098112 ]
  3. Link [Link]
External Links
ATC CodesL01XE14
AHFS Codes
  • 10:00
PDB EntriesNot Available
FDA labelDownload (326 KB)
MSDSDownload (97.1 KB)
Interactions
Drug Interactions
Drug
AbirateroneThe serum concentration of Bosutinib can be increased when it is combined with Abiraterone.
Aluminum hydroxideThe serum concentration of Bosutinib can be decreased when it is combined with Aluminum hydroxide.
AmiodaroneThe serum concentration of Bosutinib can be increased when it is combined with Amiodarone.
AprepitantThe serum concentration of Bosutinib can be increased when it is combined with Aprepitant.
AtazanavirThe serum concentration of Bosutinib can be increased when it is combined with Atazanavir.
AtorvastatinThe serum concentration of Bosutinib can be increased when it is combined with Atorvastatin.
AzithromycinThe serum concentration of Bosutinib can be increased when it is combined with Azithromycin.
BexaroteneThe serum concentration of Bosutinib can be decreased when it is combined with Bexarotene.
BoceprevirThe serum concentration of Bosutinib can be increased when it is combined with Boceprevir.
BosentanThe serum concentration of Bosutinib can be decreased when it is combined with Bosentan.
Calcium carbonateThe serum concentration of Bosutinib can be decreased when it is combined with Calcium carbonate.
CarbamazepineThe serum concentration of Bosutinib can be decreased when it is combined with Carbamazepine.
CarvedilolThe serum concentration of Bosutinib can be increased when it is combined with Carvedilol.
CeritinibThe serum concentration of Bosutinib can be increased when it is combined with Ceritinib.
CimetidineThe serum concentration of Bosutinib can be decreased when it is combined with Cimetidine.
CitalopramBosutinib may increase the QTc-prolonging activities of Citalopram.
ClarithromycinThe serum concentration of Bosutinib can be increased when it is combined with Clarithromycin.
ClozapineThe risk or severity of adverse effects can be increased when Bosutinib is combined with Clozapine.
CobicistatThe serum concentration of Bosutinib can be increased when it is combined with Cobicistat.
ConivaptanThe serum concentration of Bosutinib can be increased when it is combined with Conivaptan.
CrizotinibThe serum concentration of Bosutinib can be increased when it is combined with Crizotinib.
CyclosporineThe serum concentration of Bosutinib can be increased when it is combined with Cyclosporine.
DabrafenibThe serum concentration of Bosutinib can be decreased when it is combined with Dabrafenib.
DaclatasvirThe serum concentration of Bosutinib can be increased when it is combined with Daclatasvir.
DarunavirThe serum concentration of Bosutinib can be increased when it is combined with Darunavir.
DasatinibThe serum concentration of Bosutinib can be increased when it is combined with Dasatinib.
DeferasiroxThe serum concentration of Bosutinib can be decreased when it is combined with Deferasirox.
DelavirdineThe serum concentration of Bosutinib can be increased when it is combined with Delavirdine.
DexamethasoneThe serum concentration of Bosutinib can be decreased when it is combined with Dexamethasone.
DiltiazemThe serum concentration of Bosutinib can be increased when it is combined with Diltiazem.
DipyridamoleThe serum concentration of Bosutinib can be increased when it is combined with Dipyridamole.
DofetilideBosutinib may increase the QTc-prolonging activities of Dofetilide.
DronedaroneThe serum concentration of Bosutinib can be increased when it is combined with Dronedarone.
EfavirenzThe serum concentration of Bosutinib can be decreased when it is combined with Efavirenz.
EliglustatThe serum concentration of Bosutinib can be increased when it is combined with Eliglustat.
EnzalutamideThe serum concentration of Bosutinib can be decreased when it is combined with Enzalutamide.
ErythromycinThe serum concentration of Bosutinib can be increased when it is combined with Erythromycin.
Eslicarbazepine acetateThe serum concentration of Bosutinib can be decreased when it is combined with Eslicarbazepine acetate.
EsomeprazoleThe serum concentration of Bosutinib can be decreased when it is combined with Esomeprazole.
EtravirineThe serum concentration of Bosutinib can be decreased when it is combined with Etravirine.
FamotidineThe serum concentration of Bosutinib can be decreased when it is combined with Famotidine.
FlibanserinThe serum concentration of Bosutinib can be increased when it is combined with Flibanserin.
FluconazoleThe serum concentration of Bosutinib can be increased when it is combined with Fluconazole.
FosamprenavirThe serum concentration of Bosutinib can be increased when it is combined with Fosamprenavir.
FosaprepitantThe serum concentration of Bosutinib can be increased when it is combined with Fosaprepitant.
FosphenytoinThe serum concentration of Bosutinib can be decreased when it is combined with Fosphenytoin.
Fusidic AcidThe serum concentration of Bosutinib can be increased when it is combined with Fusidic Acid.
GoserelinBosutinib may increase the QTc-prolonging activities of Goserelin.
IbrutinibThe serum concentration of Bosutinib can be increased when it is combined with Ibrutinib.
IdelalisibThe serum concentration of Bosutinib can be increased when it is combined with Idelalisib.
ImatinibThe serum concentration of Bosutinib can be increased when it is combined with Imatinib.
IndinavirThe serum concentration of Bosutinib can be increased when it is combined with Indinavir.
IsavuconazoniumThe serum concentration of Bosutinib can be increased when it is combined with Isavuconazonium.
ItraconazoleThe serum concentration of Bosutinib can be increased when it is combined with Itraconazole.
IvacaftorThe serum concentration of Bosutinib can be increased when it is combined with Ivacaftor.
KetoconazoleThe serum concentration of Bosutinib can be increased when it is combined with Ketoconazole.
LansoprazoleThe serum concentration of Bosutinib can be decreased when it is combined with Lansoprazole.
LapatinibThe serum concentration of Bosutinib can be increased when it is combined with Lapatinib.
LeuprolideBosutinib may increase the QTc-prolonging activities of Leuprolide.
LomitapideThe serum concentration of Bosutinib can be increased when it is combined with Lomitapide.
LuliconazoleThe serum concentration of Bosutinib can be increased when it is combined with Luliconazole.
Magnesium hydroxideThe serum concentration of Bosutinib can be decreased when it is combined with Magnesium hydroxide.
Magnesium oxideThe serum concentration of Bosutinib can be decreased when it is combined with Magnesium oxide.
MefloquineThe serum concentration of Bosutinib can be increased when it is combined with Mefloquine.
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Bosutinib.
MifepristoneThe serum concentration of Bosutinib can be increased when it is combined with Mifepristone.
MirabegronThe serum concentration of Bosutinib can be increased when it is combined with Mirabegron.
MitotaneThe serum concentration of Bosutinib can be decreased when it is combined with Mitotane.
ModafinilThe serum concentration of Bosutinib can be decreased when it is combined with Modafinil.
NafcillinThe serum concentration of Bosutinib can be decreased when it is combined with Nafcillin.
NefazodoneThe serum concentration of Bosutinib can be increased when it is combined with Nefazodone.
NelfinavirThe serum concentration of Bosutinib can be increased when it is combined with Nelfinavir.
NicardipineThe serum concentration of Bosutinib can be increased when it is combined with Nicardipine.
NilotinibThe serum concentration of Bosutinib can be increased when it is combined with Nilotinib.
NizatidineThe serum concentration of Bosutinib can be decreased when it is combined with Nizatidine.
OmeprazoleThe serum concentration of Bosutinib can be decreased when it is combined with Omeprazole.
PalbociclibThe serum concentration of Bosutinib can be increased when it is combined with Palbociclib.
PantoprazoleThe serum concentration of Bosutinib can be decreased when it is combined with Pantoprazole.
PhenobarbitalThe serum concentration of Bosutinib can be decreased when it is combined with Phenobarbital.
PhenytoinThe serum concentration of Bosutinib can be decreased when it is combined with Phenytoin.
PosaconazoleThe serum concentration of Bosutinib can be increased when it is combined with Posaconazole.
PrimidoneThe serum concentration of Bosutinib can be decreased when it is combined with Primidone.
ProgesteroneThe serum concentration of Bosutinib can be increased when it is combined with Progesterone.
PropranololThe serum concentration of Bosutinib can be increased when it is combined with Propranolol.
QuinidineThe serum concentration of Bosutinib can be increased when it is combined with Quinidine.
QuinineThe serum concentration of Bosutinib can be increased when it is combined with Quinine.
RabeprazoleThe serum concentration of Bosutinib can be decreased when it is combined with Rabeprazole.
RanitidineThe serum concentration of Bosutinib can be decreased when it is combined with Ranitidine.
RanolazineThe serum concentration of Bosutinib can be increased when it is combined with Ranolazine.
ReserpineThe serum concentration of Bosutinib can be increased when it is combined with Reserpine.
RifabutinThe serum concentration of Bosutinib can be decreased when it is combined with Rifabutin.
RifampicinThe serum concentration of Bosutinib can be decreased when it is combined with Rifampicin.
RifapentineThe serum concentration of Bosutinib can be decreased when it is combined with Rifapentine.
RitonavirThe serum concentration of Bosutinib can be increased when it is combined with Ritonavir.
RolapitantThe serum concentration of Bosutinib can be increased when it is combined with Rolapitant.
SaquinavirThe serum concentration of Bosutinib can be increased when it is combined with Saquinavir.
SiltuximabThe serum concentration of Bosutinib can be decreased when it is combined with Siltuximab.
SimeprevirThe serum concentration of Bosutinib can be increased when it is combined with Simeprevir.
Sodium bicarbonateThe serum concentration of Bosutinib can be decreased when it is combined with Sodium bicarbonate.
St. John's WortThe serum concentration of Bosutinib can be decreased when it is combined with St. John's Wort.
StiripentolThe serum concentration of Bosutinib can be increased when it is combined with Stiripentol.
SunitinibThe serum concentration of Bosutinib can be increased when it is combined with Sunitinib.
TacrolimusThe serum concentration of Bosutinib can be increased when it is combined with Tacrolimus.
TamoxifenThe serum concentration of Bosutinib can be increased when it is combined with Tamoxifen.
TelaprevirThe serum concentration of Bosutinib can be increased when it is combined with Telaprevir.
TelithromycinThe serum concentration of Bosutinib can be increased when it is combined with Telithromycin.
TesmilifeneThe serum concentration of Bosutinib can be decreased when it is combined with Tesmilifene.
TocilizumabThe serum concentration of Bosutinib can be decreased when it is combined with Tocilizumab.
VandetanibThe serum concentration of Bosutinib can be increased when it is combined with Vandetanib.
VemurafenibThe serum concentration of Bosutinib can be increased when it is combined with Vemurafenib.
VerapamilThe serum concentration of Bosutinib can be increased when it is combined with Verapamil.
VoriconazoleThe serum concentration of Bosutinib can be increased when it is combined with Voriconazole.
Food Interactions
  • When given with a high fat meal, the Cmax and AUC of bosutinib increased 1.8- and 1.7-fold, respectively.

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Rho guanyl-nucleotide exchange factor activity
Specific Function:
GTPase-activating protein for RAC1 and CDC42. Promotes the exchange of RAC or CDC42-bound GDP by GTP, thereby activating them. Displays serine/threonine kinase activity.
Gene Name:
BCR
Uniprot ID:
P11274
Molecular Weight:
142818.07 Da
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
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 and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 ...
Gene Name:
ABL1
Uniprot ID:
P00519
Molecular Weight:
122871.435 Da
Kind
Protein
Organism
Human
Pharmacological action
unknown
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, responses to growth factors and cytokines, integrin signaling, but also responses to DNA damage and genotoxic agents. Functions primarily as negative regulator, but can also function as activator, depending ...
Gene Name:
LYN
Uniprot ID:
P07948
Molecular Weight:
58573.595 Da
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, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration. Acts downstream of receptors that bind the Fc region of immuno...
Gene Name:
HCK
Uniprot ID:
P08631
Molecular Weight:
59599.355 Da
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 receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling pathways that control a diverse spectrum of biological activities including...
Gene Name:
SRC
Uniprot ID:
P12931
Molecular Weight:
59834.295 Da
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Metal ion binding
Specific Function:
Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis. Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, EZH2. Interacts with cyclins A, B1, B3, D, or E. Triggers duplication of centrosomes and DNA. Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synt...
Gene Name:
CDK2
Uniprot ID:
P24941
Molecular Weight:
33929.215 Da
References
  1. Remsing Rix LL, Rix U, Colinge J, Hantschel O, Bennett KL, Stranzl T, Muller A, Baumgartner C, Valent P, Augustin M, Till JH, Superti-Furga G: Global target profile of the kinase inhibitor bosutinib in primary chronic myeloid leukemia cells. Leukemia. 2009 Mar;23(3):477-85. doi: 10.1038/leu.2008.334. Epub 2008 Nov 27. [PubMed:19039322 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Receptor signaling protein tyrosine phosphatase activity
Specific Function:
Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2...
Gene Name:
MAP2K1
Uniprot ID:
Q02750
Molecular Weight:
43438.65 Da
References
  1. Remsing Rix LL, Rix U, Colinge J, Hantschel O, Bennett KL, Stranzl T, Muller A, Baumgartner C, Valent P, Augustin M, Till JH, Superti-Furga G: Global target profile of the kinase inhibitor bosutinib in primary chronic myeloid leukemia cells. Leukemia. 2009 Mar;23(3):477-85. doi: 10.1038/leu.2008.334. Epub 2008 Nov 27. [PubMed:19039322 ]
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
Molecular Weight:
44423.735 Da
References
  1. Remsing Rix LL, Rix U, Colinge J, Hantschel O, Bennett KL, Stranzl T, Muller A, Baumgartner C, Valent P, Augustin M, Till JH, Superti-Furga G: Global target profile of the kinase inhibitor bosutinib in primary chronic myeloid leukemia cells. Leukemia. 2009 Mar;23(3):477-85. doi: 10.1038/leu.2008.334. Epub 2008 Nov 27. [PubMed:19039322 ]
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-run dynamics.
Gene Name:
MAP3K2
Uniprot ID:
Q9Y2U5
Molecular Weight:
69740.21 Da
References
  1. Ahmad S, Hughes MA, Johnson GL, Scott JE: Development and validation of a high-throughput intrinsic ATPase activity assay for the discovery of MEKK2 inhibitors. J Biomol Screen. 2013 Apr;18(4):388-99. doi: 10.1177/1087057112466430. Epub 2012 Nov 7. [PubMed:23134735 ]
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 skeletal muscle and may function in dendritic spine and synapse formation and neuronal plasticity. In slow-twitch muscles, is involved in regulation of sarcoplasmic reticulum (SR) Ca(2+) transport and in fa...
Gene Name:
CAMK2G
Uniprot ID:
Q13555
Molecular Weight:
62608.655 Da
References
  1. Amsberg GK, Koschmieder S: Profile of bosutinib and its clinical potential in the treatment of chronic myeloid leukemia. Onco Targets Ther. 2013;6:99-106. doi: 10.2147/OTT.S19901. Epub 2013 Mar 4. [PubMed:23493838 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
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Drug created on March 19, 2008 10:41 / Updated on July 27, 2016 01:57