axitinib

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Ligands
axitinib

GtoPdb Ligand ID: 5659

Synonyms: AG 013736 | AG-013736 | AG013736 | Inlyta®

axitinib is an approved drug (FDA and EMA (2012))

Comment: Axitinib is a Type-1 kinase inhibitor. Axitinib inhibits several receptor tyrosine kinases including VEGFR-1, VEGFR-2, VEGFR-3, platelet derived growth factor receptor (PDGFR), and cKIT.

View interactive charts of activity data across species

View more information in the IUPHAR Pharmacology Education Project: axitinib

axitinib is commercially available from our sponsors

2D Structure

Physico-chemical Properties

Hydrogen bond acceptors	4
Hydrogen bond donors	2
Rotatable bonds	6
Topological polar surface area	95.97
Molecular weight	386.12
XLogP	4.71
No. Lipinski's rules broken	0

SMILES / InChI / InChIKey

Canonical SMILES	CNC(=O)c1ccccc1Sc1ccc2c(c1)[nH]nc2C=Cc1ccccn1
Isomeric SMILES	CNC(=O)c1ccccc1Sc1ccc2c(c1)[nH]nc2/C=C/c1ccccn1
InChI	InChI=1S/C22H18N4OS/c1-23-22(27)18-7-2-3-8-21(18)28-16-10-11-17-19(25-26-20(17)14-16)12-9-15-6-4-5-13-24-15/h2-14H,1H3,(H,23,27)(H,25,26)/b12-9+
InChI Key	RITAVMQDGBJQJZ-FMIVXFBMSA-N

No information available.

No information available.

Summary of Clinical Use
Approved for the treatment of advanced renal cell carcinoma after failure of one prior systemic therapy.

Summary of Clinical Use

Approved for the treatment of advanced renal cell carcinoma after failure of one prior systemic therapy.

Mechanism Of Action and Pharmacodynamic Effects
Axitinib is a potent and selective, orally administered tyrosine kinase inhibitor of vascular endothelial growth factor receptors (VEGFR)-1, -2 and -3 which are implicated in pathologic angiogenesis, tumour growth, and metastatic progression of cancer. By blocking these receptors ataxinib prevents the progression of cancer by inhibiting angiogenesis and blocking tumour growth.

Mechanism Of Action and Pharmacodynamic Effects

Axitinib is a potent and selective, orally administered tyrosine kinase inhibitor of vascular endothelial growth factor receptors (VEGFR)-1, -2 and -3 which are implicated in pathologic angiogenesis, tumour growth, and metastatic progression of cancer. By blocking these receptors ataxinib prevents the progression of cancer by inhibiting angiogenesis and blocking tumour growth.

Pharmacokinetics
Absorption/Distribution
A 5mg dose reaches maximum plasma concentration within 4 hours of administration. Bioavailability is 58%, with >99% bound to plasma proteins, primarily albumin with the remainder bound to α1-acid glycoprotein.
Biotransformation/Metabolism
Axitinib undergoes metabolism mainly in the liver, with CYP3A4 and CYP3A5 being the primary hepatic enzymes involved with secondary contribution from CYP1A2, CYP2C19, and UGT1A1.
Elimination
Axitinib is mainly eliminated unchanged in the feces (41%) with 12% of the original dose as unchanged axitinib. 23% is eliminated in the urine, most of which is metabolites.
Population pharmacokinetics
Axitinib pharmacokinetics are not significantly affected by age, body weight, gender or ethnicity in tested populations. Axitinib has not been studied in patients <18 years of age. Renal function, UGT1A1 genotype, or CYP2C19 genotype also have no effect.
Organ function impairment
In vitro and in vivo data indicate that axitinib is primarily metabolised by the liver. Patients with Child-Pugh class A and B hepatic impairmant require no dose adjustment. However, as this drug has not been studied in subjects with severe hepatic impairment (Child-Pugh class C) it should not be used in this population. Mild to severe renal impairment has no significant effect on the pharmacokinetics of axitinib. High levels of exposures up to two-fold greater than therapeutic levels expected following a 5 mg dose, do not produce clinically-significant QT interval prolongation.

Pharmacokinetics

Absorption/Distribution

A 5mg dose reaches maximum plasma concentration within 4 hours of administration. Bioavailability is 58%, with >99% bound to plasma proteins, primarily albumin with the remainder bound to α1-acid glycoprotein.

Biotransformation/Metabolism

Axitinib undergoes metabolism mainly in the liver, with CYP3A4 and CYP3A5 being the primary hepatic enzymes involved with secondary contribution from CYP1A2, CYP2C19, and UGT1A1.

Elimination

Axitinib is mainly eliminated unchanged in the feces (41%) with 12% of the original dose as unchanged axitinib. 23% is eliminated in the urine, most of which is metabolites.

Population pharmacokinetics

Axitinib pharmacokinetics are not significantly affected by age, body weight, gender or ethnicity in tested populations. Axitinib has not been studied in patients <18 years of age. Renal function, UGT1A1 genotype, or CYP2C19 genotype also have no effect.

Organ function impairment

In vitro and in vivo data indicate that axitinib is primarily metabolised by the liver. Patients with Child-Pugh class A and B hepatic impairmant require no dose adjustment. However, as this drug has not been studied in subjects with severe hepatic impairment (Child-Pugh class C) it should not be used in this population. Mild to severe renal impairment has no significant effect on the pharmacokinetics of axitinib. High levels of exposures up to two-fold greater than therapeutic levels expected following a 5 mg dose, do not produce clinically-significant QT interval prolongation.