Ponatinib

Identification

Summary

Ponatinib is a kinase inhibitor used to treat patients with various types of chronic myeloid leukemia (CML).

Brand Names
Iclusig
Generic Name
Ponatinib
DrugBank Accession Number
DB08901
Background

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.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 532.5595
Monoisotopic: 532.219844131
Chemical Formula
C29H27F3N6O
Synonyms
  • Ponatinib
  • Ponatinibum
External IDs
  • AP 24534
  • AP-24534
  • AP24534

Pharmacology

Indication

Ponatinib 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.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofAccelerated phase chronic myeloid leukemia••••••••••••
Treatment ofAcute lymphoblastic leukemia••••••••••••
Treatment ofChronic phase chronic myeloid leukemia••••••••••••
Treatment ofBlast phase chronic myeloid leukemia••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Not Available

Mechanism of action

Ponatinib 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.

TargetActionsOrganism
ATyrosine-protein kinase ABL1
inhibitor
Humans
ABreakpoint cluster region protein
inhibitor
Humans
UMast/stem cell growth factor receptor Kit
inhibitor
Humans
UProto-oncogene tyrosine-protein kinase receptor Ret
inhibitor
Humans
UAngiopoietin-1 receptor
inhibitor
Humans
UReceptor-type tyrosine-protein kinase FLT3
inhibitor
Humans
UFibroblast growth factor receptor 1
inhibitor
Humans
UFibroblast growth factor receptor 2
inhibitor
Humans
UFibroblast growth factor receptor 3
inhibitor
Humans
UFibroblast growth factor receptor 4
inhibitor
Humans
UTyrosine-protein kinase Lck
inhibitor
Humans
UProto-oncogene tyrosine-protein kinase Src
inhibitor
Humans
UTyrosine-protein kinase Lyn
inhibitor
Humans
UVascular endothelial growth factor receptor 2
inhibitor
Humans
UPlatelet-derived growth factor receptor alpha
inhibitor
Humans
Absorption

The 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 elimination

Ponatinib 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-life

After 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).

Clearance

Not Available

Adverse Effects
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Toxicity

The 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.

Pathways
PathwayCategory
Ponatinib Inhibition of BCR-ABLDrug action
Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbametapirThe serum concentration of Ponatinib can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Ponatinib can be increased when combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Ponatinib.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Ponatinib.
AbirateroneThe metabolism of Ponatinib can be decreased when combined with Abiraterone.
Food Interactions
  • Avoid St. John's Wort. This herb induces the CYP3A4 metabolism of ponatinib and may reduce its serum concentration.
  • Exercise caution with grapefruit products. If coadministration of ponatinib and grapefruit is necessary, reduce the dose of ponatinib.
  • Take with or without food.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Ponatinib hydrochloride96R6PU3D8J1114544-31-8BWTNNZPNKQIADY-UHFFFAOYSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
IclusigTablet, film coated45 mg/1OralTakeda Pharmaceuticals America, Inc.2012-12-14Not applicableUS flag
IclusigTablet, film coated45 mg/1OralAriad Pharmaceuticals2012-12-142020-07-26US flag
IclusigTablet45 mgOralIncyte Biosciences Distribution B.V.2021-02-09Not applicableEU flag
IclusigTablet15 mgOralIncyte Biosciences Distribution B.V.2021-02-09Not applicableEU flag
IclusigTablet, film coated10 mg/1OralTakeda Pharmaceuticals America, Inc.2021-01-11Not applicableUS flag

Categories

ATC Codes
L01EA05 — Ponatinib
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as benzanilides. These are aromatic compounds containing an anilide group in which the carboxamide group is substituted with a benzene ring. They have the general structure RNC(=O)R', where R,R'= benzene.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Anilides
Direct Parent
Benzanilides
Alternative Parents
Trifluoromethylbenzenes / p-Toluamides / Benzamides / Benzoyl derivatives / Benzylamines / Phenylmethylamines / N-methylpiperazines / Aralkylamines / N-substituted imidazoles / Pyridazines and derivatives
show 11 more
Substituents
1,4-diazinane / Alkyl fluoride / Alkyl halide / Amine / Amino acid or derivatives / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Azole / Benzamide
show 31 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
benzamides, acetylenic compound, N-methylpiperazine, (trifluoromethyl)benzenes, imidazopyridazine (CHEBI:78543)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
4340891KFS
CAS number
943319-70-8
InChI Key
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

References

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. [Article]
Human Metabolome Database
HMDB0240214
KEGG Drug
D09950
PubChem Compound
24826799
PubChem Substance
175427142
ChemSpider
24747381
BindingDB
50322535
RxNav
1364347
ChEBI
78543
ChEMBL
CHEMBL1171837
ZINC
ZINC000036701290
PharmGKB
PA165980594
PDBe Ligand
0LI
Drugs.com
Drugs.com Drug Page
Wikipedia
Ponatinib
PDB Entries
3oxz / 3zos / 4c8b / 4qrc / 4tyj / 4u0i / 4uxq / 4v01 / 4v04 / 6eg9
show 4 more
FDA label
Download (295 KB)
MSDS
Download (98 KB)

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
TabletOral
TabletOral30 mg
TabletOral45 mg
Tablet, film coatedOral10 mg/1
Tablet, film coatedOral15 mg/1
Tablet, film coatedOral30 mg/1
Tablet, film coatedOral30 MG
Tablet, film coatedOral45 mg/1
TabletOral15 mg
Tablet, film coatedOral45 mg
Tablet, film coatedOral
Tablet, film coatedOral15 MG
Tablet, coatedOral
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US9029533No2015-05-122026-12-22US flag
US8114874No2012-02-142026-12-22US flag
US9493470No2016-11-152033-12-12US flag
US11192897No2021-12-072033-12-12US flag
US11192895No2021-12-072033-12-12US flag
US11384086No2013-12-122033-12-12US flag

Properties

State
Solid
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)15.37Chemaxon
pKa (Strongest Basic)7.62Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count5Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area65.77 Å2Chemaxon
Rotatable Bond Count7Chemaxon
Refractivity152.63 m3·mol-1Chemaxon
Polarizability55.39 Å3Chemaxon
Number of Rings5Chemaxon
Bioavailability1Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
MS/MS Spectrum - , positiveLC-MS/MSsplash10-014i-1490100000-181c36e7111f139a09cd
MS/MS Spectrum - , positiveLC-MS/MSsplash10-03e9-0290150000-ab2ecf1ddb48e116ad86
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-01q9-0040090000-929c8e39e27a0938c4fb
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-01q9-0010290000-f18b4421930410667175
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-03di-0290120000-4e299b991f31e4ab9963
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0uk9-0390370000-ab4cdadc0c9b33713b4e
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-01q9-0090020000-ba9a12a2612d1cee9323
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-03di-0000390000-21a8992a8476c95f348d
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-263.6107224
predicted
DarkChem Lite v0.1.0
[M-H]-210.82472
predicted
DeepCCS 1.0 (2019)
[M+H]+263.5184224
predicted
DarkChem Lite v0.1.0
[M+H]+213.22029
predicted
DeepCCS 1.0 (2019)
[M+Na]+262.5274224
predicted
DarkChem Lite v0.1.0
[M+Na]+219.13283
predicted
DeepCCS 1.0 (2019)

Targets

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Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
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Kind
Protein
Organism
Humans
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 a...
Gene Name
ABL1
Uniprot ID
P00519
Uniprot Name
Tyrosine-protein kinase ABL1
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. [Article]
Kind
Protein
Organism
Humans
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
Uniprot Name
Breakpoint cluster region protein
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. [Article]
Kind
Protein
Organism
Humans
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. 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. [Article]
Kind
Protein
Organism
Humans
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. 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. [Article]
Kind
Protein
Organism
Humans
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
Kind
Protein
Organism
Humans
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. 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. [Article]
Kind
Protein
Organism
Humans
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. 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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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. 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. [Article]
Kind
Protein
Organism
Humans
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. 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. [Article]
Kind
Protein
Organism
Humans
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 o...
Gene Name
FGFR4
Uniprot ID
P22455
Uniprot Name
Fibroblast growth factor receptor 4
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. [Article]
Kind
Protein
Organism
Humans
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. 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. [Article]
Kind
Protein
Organism
Humans
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. 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. [Article]
Kind
Protein
Organism
Humans
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. 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. [Article]
Kind
Protein
Organism
Humans
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. 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. [Article]
Kind
Protein
Organism
Humans
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. 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. [Article]

Enzymes

Kind
Protein
Organism
Humans
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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 un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
Kind
Protein
Organism
Humans
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...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Lin, Kostov R, Huang JT, Henderson CJ, Wolf CR: Novel Pathways of Ponatinib Disposition Catalyzed By CYP1A1 Involving Generation of Potentially Toxic Metabolites. J Pharmacol Exp Ther. 2017 Oct;363(1):12-19. doi: 10.1124/jpet.117.243246. [Article]
Kind
Protein
Organism
Humans
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 un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Price KE, Saleem N, Lee G, Steinberg M: Potential of ponatinib to treat chronic myeloid leukemia and acute lymphoblastic leukemia. Onco Targets Ther. 2013 Aug 20;6:1111-8. doi: 10.2147/OTT.S36980. eCollection 2013. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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

Drug created at June 08, 2013 22:03 / Updated at January 02, 2024 23:48