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Identification
NamePonatinib
Accession NumberDB08901
TypeSmall Molecule
GroupsApproved
Description

Ponatinib is a novel Bcr-Abl tyrosine kinase inhibitor that is especially effective against the T315I mutation for the treatment of chronic myeloid leukemia. FDA approved on December 14, 2012.

Structure
Thumb
Synonyms
AP 24534
AP24534
Ponatinibum
External Identifiers
  • AP24534
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Iclusigtablet, film coated30 mg/1oralARIAD Pharmaceuticals, Inc.2015-04-22Not applicableUs
Iclusigtablet45 mgoralAriad Pharmaceuticals Inc2016-01-07Not applicableCanada
Iclusigtablet15 mgoralAriad Pharmaceuticals Inc2015-08-21Not applicableCanada
Iclusigtablet, film coated15 mg/1oralARIAD Pharmaceuticals, Inc.2012-12-14Not applicableUs
Iclusigtablet, film coated45 mg/1oralARIAD Pharmaceuticals, Inc.2012-12-14Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Ponatinib Hydrochloride
Thumb
  • InChI Key: BWTNNZPNKQIADY-UHFFFAOYSA-N
  • Monoisotopic Mass: 568.19652187
  • Average Mass: 569.02
DBSALT000142
Categories
UNII4340891KFS
CAS number943319-70-8
WeightAverage: 532.5595
Monoisotopic: 532.219844131
Chemical FormulaC29H27F3N6O
InChI KeyInChIKey=PHXJVRSECIGDHY-UHFFFAOYSA-N
InChI
InChI=1S/C29H27F3N6O/c1-20-5-6-22(16-21(20)8-10-25-18-33-27-4-3-11-34-38(25)27)28(39)35-24-9-7-23(26(17-24)29(30,31)32)19-37-14-12-36(2)13-15-37/h3-7,9,11,16-18H,12-15,19H2,1-2H3,(H,35,39)
IUPAC Name
3-(2-{imidazo[1,2-b]pyridazin-3-yl}ethynyl)-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide
SMILES
CN1CCN(CC2=CC=C(NC(=O)C3=CC(C#CC4=CN=C5C=CC=NN45)=C(C)C=C3)C=C2C(F)(F)F)CC1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as n-phenylbenzamides. These are benzamides that are N-linked to a phenyl group via the carboxamide group.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzamides
Direct ParentN-phenylbenzamides
Alternative Parents
Substituents
  • N-phenylbenzamide
  • N-arylamide
  • Benzoic acid or derivatives
  • Phenylmethylamine
  • Benzylamine
  • Benzoyl
  • Aralkylamine
  • N-alkylpiperazine
  • N-methylpiperazine
  • Toluene
  • Pyridazine
  • Piperazine
  • N-substituted imidazole
  • 1,4-diazinane
  • Heteroaromatic compound
  • Imidazole
  • Azole
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Carbonyl group
  • Amine
  • Alkyl halide
  • Alkyl fluoride
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationPonatinib is indicated for the treatment of adult patients with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia (CML) that is resistant or intolerant to prior tyrosine kinase inhibitor therapy or Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL) that is resistant or intolerant to prior tyrosine kinase inhibitor therapy.
PharmacodynamicsNot Available
Mechanism of actionPonatinib is a multi-target kinase inhibitor. Its primary cellular target is the Bcr-Abl tyrosine kinase protein which is constitutively active and promotes the progression of CML. This protein arises from the fused Bcr and Abl gene- what is commonly known as the Philadelphia chromosome. Ponatinib is unique in that it is especially useful in the treatment of resistant CML because it inhibits the tyrosine kinase activity of Abl and T315I mutant kinases. The T315I mutation confers resistance in cells as it prevents other Bcr-Abl inhibitors from binding to the Abl kinase. Other targets that ponatinib inhibits are members of the VEGFR, PDGFR, FGFR, EPH receptors and SRC families of kinases, and KIT, RET, TIE2, and FLT3. A decrease in tumour size expressing native or T315I mutant BCR-ABL have been observed in rats.
Related Articles
AbsorptionThe absolute bioavailability of ponatinib is unknown. Peak concentrations of ponatinib are observed within 6 hours after Iclusig oral administration. Food does not affect absorption of food. The aqueous solubility of ponatinib is pH dependent, with higher pH resulting in lower solubility. When 45 mg of ponatinib is given to cancer patients, the pharmacokinetic parameters are as follows: Cmax = 73 ng/mL; AUC = 1253 ng•hr/mL;
Volume of distribution

After oral administration of 45 mg ponatinib once daily for 28 days in cancer patients, the steady state volume of distribution is 1223 L. Ponatinib is a weak substrate for P-gp and ABCG2.

Protein binding> 99% bound to plasma proteins.
Metabolism

At least 64% of a ponatinib dose undergoes phase I and phase II metabolism. CYP3A4 and to a lesser extent CYP2C8, CYP2D6 and CYP3A5 are involved in the phase I metabolism of ponatinib in vitro. Ponatinib is also metabolized by esterases and/or amidases.

Route of eliminationPonatinib is mainly eliminated via feces. Following a single oral dose of [14C]-labeled ponatinib, approximately 87% of the radioactive dose is recovered in the feces and approximately 5% in the urine.
Half lifeAfter oral administration of 45 mg ponatinib once daily for 28 days in cancer patients, the terminal elimination half-life is 24 hours (range of 12 - 66 hours).
ClearanceNot Available
ToxicityThe most common non-hematologic adverse reactions (≥ 20%) were hypertension, rash, abdominal pain, fatigue, headache, dry skin, constipation, arthralgia, nausea, and pyrexia. Hematologic adverse reactions included thrombocytopenia, anemia, neutropenia, lymphopenia, and leukopenia.
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+1.0
Blood Brain Barrier+0.9444
Caco-2 permeable-0.5985
P-glycoprotein substrateSubstrate0.7205
P-glycoprotein inhibitor IInhibitor0.8197
P-glycoprotein inhibitor IIInhibitor0.9125
Renal organic cation transporterInhibitor0.5
CYP450 2C9 substrateNon-substrate0.8612
CYP450 2D6 substrateNon-substrate0.7047
CYP450 3A4 substrateSubstrate0.7636
CYP450 1A2 substrateNon-inhibitor0.8592
CYP450 2C9 inhibitorNon-inhibitor0.6804
CYP450 2D6 inhibitorNon-inhibitor0.764
CYP450 2C19 inhibitorInhibitor0.5563
CYP450 3A4 inhibitorNon-inhibitor0.5613
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6686
Ames testNon AMES toxic0.5331
CarcinogenicityNon-carcinogens0.8254
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.8377 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8253
hERG inhibition (predictor II)Inhibitor0.7493
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Tabletoral15 mg
Tabletoral45 mg
Tablet, film coatedoral15 mg/1
Tablet, film coatedoral30 mg/1
Tablet, film coatedoral45 mg/1
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8114874 No2006-12-222026-12-22Us
US9029533 No2006-12-222026-12-22Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
pKa2.77 and 7.8 FDA label
Predicted Properties
PropertyValueSource
Water Solubility0.00295 mg/mLALOGPS
logP3.94ALOGPS
logP4.97ChemAxon
logS-5.3ALOGPS
pKa (Strongest Acidic)11.36ChemAxon
pKa (Strongest Basic)8.03ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area65.77 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity152.63 m3·mol-1ChemAxon
Polarizability55.69 Å3ChemAxon
Number of Rings5ChemAxon
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. Reddy EP, Aggarwal AK: The ins and outs of bcr-abl inhibition. Genes Cancer. 2012 May;3(5-6):447-54. doi: 10.1177/1947601912462126. [PubMed:23226582 ]
External Links
ATC CodesL01XE24
AHFS Codes
  • 10:00
PDB EntriesNot Available
FDA labelDownload (295 KB)
MSDSDownload (98 KB)
Interactions
Drug Interactions
Drug
AtazanavirThe serum concentration of Ponatinib can be increased when it is combined with Atazanavir.
BoceprevirThe serum concentration of Ponatinib can be increased when it is combined with Boceprevir.
CarbamazepineThe serum concentration of Ponatinib can be decreased when it is combined with Carbamazepine.
CeritinibThe serum concentration of Ponatinib can be increased when it is combined with Ceritinib.
ClarithromycinThe serum concentration of Ponatinib can be increased when it is combined with Clarithromycin.
ClozapineThe risk or severity of adverse effects can be increased when Ponatinib is combined with Clozapine.
CobicistatThe serum concentration of Ponatinib can be increased when it is combined with Cobicistat.
DarunavirThe serum concentration of Ponatinib can be increased when it is combined with Darunavir.
EnzalutamideThe serum concentration of Ponatinib can be decreased when it is combined with Enzalutamide.
FosphenytoinThe serum concentration of Ponatinib can be decreased when it is combined with Fosphenytoin.
IdelalisibThe serum concentration of Ponatinib can be increased when it is combined with Idelalisib.
IndinavirThe serum concentration of Ponatinib can be increased when it is combined with Indinavir.
ItraconazoleThe serum concentration of Ponatinib can be increased when it is combined with Itraconazole.
KetoconazoleThe serum concentration of Ponatinib can be increased when it is combined with Ketoconazole.
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Ponatinib.
MitotaneThe serum concentration of Ponatinib can be decreased when it is combined with Mitotane.
NefazodoneThe serum concentration of Ponatinib can be increased when it is combined with Nefazodone.
NelfinavirThe serum concentration of Ponatinib can be increased when it is combined with Nelfinavir.
PhenobarbitalThe serum concentration of Ponatinib can be decreased when it is combined with Phenobarbital.
PhenytoinThe serum concentration of Ponatinib can be decreased when it is combined with Phenytoin.
PosaconazoleThe serum concentration of Ponatinib can be increased when it is combined with Posaconazole.
PrimidoneThe serum concentration of Ponatinib can be decreased when it is combined with Primidone.
RifabutinThe serum concentration of Ponatinib can be decreased when it is combined with Rifabutin.
RifampicinThe serum concentration of Ponatinib can be decreased when it is combined with Rifampicin.
RifapentineThe serum concentration of Ponatinib can be decreased when it is combined with Rifapentine.
RitonavirThe serum concentration of Ponatinib can be increased when it is combined with Ritonavir.
SaquinavirThe serum concentration of Ponatinib can be increased when it is combined with Saquinavir.
St. John's WortThe serum concentration of Ponatinib can be decreased when it is combined with St. John's Wort.
TelaprevirThe serum concentration of Ponatinib can be increased when it is combined with Telaprevir.
TelithromycinThe serum concentration of Ponatinib can be increased when it is combined with Telithromycin.
VoriconazoleThe serum concentration of Ponatinib can be increased when it is combined with Voriconazole.
Food InteractionsNot Available

Targets

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
References
  1. Iqbal Z, Aleem A, Iqbal M, Naqvi MI, Gill A, Taj AS, Qayyum A, ur-Rehman N, Khalid AM, Shah IH, Khalid M, Haq R, Khan M, Baig SM, Jamil A, Abbas MN, Absar M, Mahmood A, Rasool M, Akhtar T: Sensitive detection of pre-existing BCR-ABL kinase domain mutations in CD34+ cells of newly diagnosed chronic-phase chronic myeloid leukemia patients is associated with imatinib resistance: implications in the post-imatinib era. PLoS One. 2013;8(2):e55717. doi: 10.1371/journal.pone.0055717. Epub 2013 Feb 8. [PubMed:23409026 ]
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
References
  1. Iqbal Z, Aleem A, Iqbal M, Naqvi MI, Gill A, Taj AS, Qayyum A, ur-Rehman N, Khalid AM, Shah IH, Khalid M, Haq R, Khan M, Baig SM, Jamil A, Abbas MN, Absar M, Mahmood A, Rasool M, Akhtar T: Sensitive detection of pre-existing BCR-ABL kinase domain mutations in CD34+ cells of newly diagnosed chronic-phase chronic myeloid leukemia patients is associated with imatinib resistance: implications in the post-imatinib era. PLoS One. 2013;8(2):e55717. doi: 10.1371/journal.pone.0055717. Epub 2013 Feb 8. [PubMed:23409026 ]
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 maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. In response to KITLG/SCF binding, KIT can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1...
Gene Name:
KIT
Uniprot ID:
P10721
Molecular Weight:
109863.655 Da
References
  1. Gleixner KV, Peter B, Blatt K, Suppan V, Reiter A, Radia D, Hadzijusufovic E, Valent P: Synergistic growth-inhibitory effects of ponatinib and midostaurin (PKC412) on neoplastic mast cells carrying KIT D816V. Haematologica. 2013 Sep;98(9):1450-7. doi: 10.3324/haematol.2012.079202. Epub 2013 Mar 28. [PubMed:23539538 ]
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 derived neurotrophic factor family ligands. Phosphorylates PTK2/FAK1. Regulates both cell death/survival balance and positional information. Required for the molecular mechanisms orchestration during in...
Gene Name:
RET
Uniprot ID:
P07949
Molecular Weight:
124317.465 Da
References
  1. De Falco V, Buonocore P, Muthu M, Torregrossa L, Basolo F, Billaud M, Gozgit JM, Carlomagno F, Santoro M: Ponatinib (AP24534) is a novel potent inhibitor of oncogenic RET mutants associated with thyroid cancer. J Clin Endocrinol Metab. 2013 May;98(5):E811-9. doi: 10.1210/jc.2012-2672. Epub 2013 Mar 22. [PubMed:23526464 ]
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, reorganization of the actin cytoskeleton, but also maintenance of vascular quiescence. Has anti-inflammatory effects by preventing the leakage of proinflammatory plasma proteins and leukocytes from ...
Gene Name:
TEK
Uniprot ID:
Q02763
Molecular Weight:
125829.005 Da
References
  1. FDA label
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. Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or...
Gene Name:
FLT3
Uniprot ID:
P36888
Molecular Weight:
112902.51 Da
References
  1. Smith CC, Lasater EA, Zhu X, Lin KC, Stewart WK, Damon LE, Salerno S, Shah NP: Activity of ponatinib against clinically-relevant AC220-resistant kinase domain mutants of FLT3-ITD. Blood. 2013 Apr 18;121(16):3165-71. doi: 10.1182/blood-2012-07-442871. Epub 2013 Feb 21. [PubMed:23430109 ]
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 and migration. Required for normal mesoderm patterning and correct axial organization during embryonic development, normal skeletogenesis and normal development of the gonadotropin-releasing hormone (...
Gene Name:
FGFR1
Uniprot ID:
P11362
Molecular Weight:
91866.935 Da
References
  1. Ren M, Hong M, Liu G, Wang H, Patel V, Biddinger P, Silva J, Cowell J, Hao Z: Novel FGFR inhibitor ponatinib suppresses the growth of non-small cell lung cancer cells overexpressing FGFR1. Oncol Rep. 2013 Jun;29(6):2181-90. doi: 10.3892/or.2013.2386. Epub 2013 Apr 4. [PubMed:23563700 ]
  2. Gozgit JM, Squillace RM, Wongchenko MJ, Miller D, Wardwell S, Mohemmad Q, Narasimhan NI, Wang F, Clackson T, Rivera VM: Combined targeting of FGFR2 and mTOR by ponatinib and ridaforolimus results in synergistic antitumor activity in FGFR2 mutant endometrial cancer models. Cancer Chemother Pharmacol. 2013 May;71(5):1315-23. doi: 10.1007/s00280-013-2131-z. Epub 2013 Mar 7. [PubMed:23468082 ]
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 apoptosis, and in the regulation of embryonic development. Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and skin development. Plays an...
Gene Name:
FGFR2
Uniprot ID:
P21802
Molecular Weight:
92024.29 Da
References
  1. Gozgit JM, Squillace RM, Wongchenko MJ, Miller D, Wardwell S, Mohemmad Q, Narasimhan NI, Wang F, Clackson T, Rivera VM: Combined targeting of FGFR2 and mTOR by ponatinib and ridaforolimus results in synergistic antitumor activity in FGFR2 mutant endometrial cancer models. Cancer Chemother Pharmacol. 2013 May;71(5):1315-23. doi: 10.1007/s00280-013-2131-z. Epub 2013 Mar 7. [PubMed:23468082 ]
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 essential role in the regulation of chondrocyte differentiation, proliferation and apoptosis, and is required for normal skeleton development. Regulates both osteogenesis and postnatal bone mineraliz...
Gene Name:
FGFR3
Uniprot ID:
P22607
Molecular Weight:
87708.905 Da
References
  1. Gozgit JM, Squillace RM, Wongchenko MJ, Miller D, Wardwell S, Mohemmad Q, Narasimhan NI, Wang F, Clackson T, Rivera VM: Combined targeting of FGFR2 and mTOR by ponatinib and ridaforolimus results in synergistic antitumor activity in FGFR2 mutant endometrial cancer models. Cancer Chemother Pharmacol. 2013 May;71(5):1315-23. doi: 10.1007/s00280-013-2131-z. Epub 2013 Mar 7. [PubMed:23468082 ]
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 a role in the regulation of cell proliferation, differentiation and migration, and in regulation of lipid metabolism, bile acid biosynthesis, glucose uptake, vitamin D metabolism and phosphate homeostasis. Required for normal down-regulation of the expression of CYP7A1, the rate-limiting enzyme in...
Gene Name:
FGFR4
Uniprot ID:
P22455
Molecular Weight:
87953.535 Da
References
  1. Gozgit JM, Squillace RM, Wongchenko MJ, Miller D, Wardwell S, Mohemmad Q, Narasimhan NI, Wang F, Clackson T, Rivera VM: Combined targeting of FGFR2 and mTOR by ponatinib and ridaforolimus results in synergistic antitumor activity in FGFR2 mutant endometrial cancer models. Cancer Chemother Pharmacol. 2013 May;71(5):1315-23. doi: 10.1007/s00280-013-2131-z. Epub 2013 Mar 7. [PubMed:23468082 ]
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-cell antigen receptor (TCR)-linked signal transduction pathways. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. Association of the TCR with a peptide antig...
Gene Name:
LCK
Uniprot ID:
P06239
Molecular Weight:
58000.15 Da
References
  1. Gushwa NN, Kang S, Chen J, Taunton J: Selective targeting of distinct active site nucleophiles by irreversible SRC-family kinase inhibitors. J Am Chem Soc. 2012 Dec 19;134(50):20214-7. doi: 10.1021/ja310659j. Epub 2012 Dec 4. [PubMed:23190395 ]
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
References
  1. O'Hare T, Shakespeare WC, Zhu X, Eide CA, Rivera VM, Wang F, Adrian LT, Zhou T, Huang WS, Xu Q, Metcalf CA 3rd, Tyner JW, Loriaux MM, Corbin AS, Wardwell S, Ning Y, Keats JA, Wang Y, Sundaramoorthi R, Thomas M, Zhou D, Snodgrass J, Commodore L, Sawyer TK, Dalgarno DC, Deininger MW, Druker BJ, Clackson T: AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell. 2009 Nov 6;16(5):401-12. doi: 10.1016/j.ccr.2009.09.028. [PubMed:19878872 ]
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, 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
References
  1. O'Hare T, Shakespeare WC, Zhu X, Eide CA, Rivera VM, Wang F, Adrian LT, Zhou T, Huang WS, Xu Q, Metcalf CA 3rd, Tyner JW, Loriaux MM, Corbin AS, Wardwell S, Ning Y, Keats JA, Wang Y, Sundaramoorthi R, Thomas M, Zhou D, Snodgrass J, Commodore L, Sawyer TK, Dalgarno DC, Deininger MW, Druker BJ, Clackson T: AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell. 2009 Nov 6;16(5):401-12. doi: 10.1016/j.ccr.2009.09.028. [PubMed:19878872 ]
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 embryonic hematopoiesis. Promotes proliferation, survival, migration and differentiation of endothelial cells. Promotes reorganization of the actin cytoskeleton. Isoforms lacking a transmembrane domai...
Gene Name:
KDR
Uniprot ID:
P35968
Molecular Weight:
151525.555 Da
References
  1. O'Hare T, Shakespeare WC, Zhu X, Eide CA, Rivera VM, Wang F, Adrian LT, Zhou T, Huang WS, Xu Q, Metcalf CA 3rd, Tyner JW, Loriaux MM, Corbin AS, Wardwell S, Ning Y, Keats JA, Wang Y, Sundaramoorthi R, Thomas M, Zhou D, Snodgrass J, Commodore L, Sawyer TK, Dalgarno DC, Deininger MW, Druker BJ, Clackson T: AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell. 2009 Nov 6;16(5):401-12. doi: 10.1016/j.ccr.2009.09.028. [PubMed:19878872 ]
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 chemotaxis. Depending on the context, promotes or inhibits cell proliferation and cell migration. Plays an important role in the differentiation of bone marrow-derived mesenchymal stem cells. Required for...
Gene Name:
PDGFRA
Uniprot ID:
P16234
Molecular Weight:
122668.46 Da
References
  1. O'Hare T, Shakespeare WC, Zhu X, Eide CA, Rivera VM, Wang F, Adrian LT, Zhou T, Huang WS, Xu Q, Metcalf CA 3rd, Tyner JW, Loriaux MM, Corbin AS, Wardwell S, Ning Y, Keats JA, Wang Y, Sundaramoorthi R, Thomas M, Zhou D, Snodgrass J, Commodore L, Sawyer TK, Dalgarno DC, Deininger MW, Druker BJ, Clackson T: AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell. 2009 Nov 6;16(5):401-12. doi: 10.1016/j.ccr.2009.09.028. [PubMed:19878872 ]

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
References
  1. FDA label
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Steroid 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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme...
Gene Name:
CYP2C8
Uniprot ID:
P10632
Molecular Weight:
55824.275 Da
References
  1. FDA label
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 Da
References
  1. FDA label
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxygen binding
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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A5
Uniprot ID:
P20815
Molecular Weight:
57108.065 Da
References
  1. FDA label

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
References
  1. FDA label
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
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 from mitochondria to cytosol and from cytosol to extracellular space, and cellular export of hemin, and heme. Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from t...
Gene Name:
ABCG2
Uniprot ID:
Q9UNQ0
Molecular Weight:
72313.47 Da
References
  1. FDA label
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Transporter activity
Specific Function:
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name:
ABCB11
Uniprot ID:
O95342
Molecular Weight:
146405.83 Da
References
  1. FDA label
Comments
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Drug created on June 08, 2013 16:03 / Updated on May 25, 2016 02:17