Chemical Properties
Off-White Solid
Uses
Pazopanib Hydrochloride (GW786034, Votrient, Armala,444731-52-6) is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFR, FGFR, c-Kit and c-Fms with IC50 of 10 nM, 30 nM, 47 nM, 84 nM, 74 nM, 140 nM and 146 nM, respectively.
Uses
Pazopanib(444731-52-6) is a potent and selective multi-targeted receptor tyrosine kinase inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFR-α/β, and c-Kit.
Uses
An oral angiogenesis inhibitor targeting VEGFR and PDGFR.
Uses
Pazopanib is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFR, FGFR, c-Kit and c-Fms with IC50 of 10 nM, 30 nM, 47 nM, 84 nM, 74 nM, 140 nM and 146 nM, respectively.
Description
Pazopanib(444731-52-6) is a multi-kinase inhibitor that inhibits the VEGF receptors VEGFR1, VEGFR2, and VEGFR3 (IC
50s = 10, 30, and 47 nM, respectively, in a cell-free enzyme assay).
1 It also inhibits PDGFRα, PDGFRβ, and c-Kit (IC
50s = 71, 84, and 74 nM, respectively, in a cell-free enzyme assay) as well as additional receptor tyrosine kinases. Pazopanib inhibits upregulation of the surface adhesion proteins ICAM-1 and VCAM-1 induced by VEGF in multiple myeloma cells cocultured with human umbilical vein endothelial cells (HUVECs) and decreases multiple myeloma cell adhesion to HUVECs.
2 It also inhibits proliferation of multiple myeloma cells cocultured with HUVECs. Pazopanib (30 and 100 mg/kg) reduces tumor growth, induces apoptosis, decreases angiogenesis, and increases survival in a multiple myeloma mouse xenograft model. Formulations containing pazopanib have been used in the treatment of cancer.
Characteristics
Class: receptor tyrosine kinase
Treatment: RCC, STS
Oral bioavailability = 14–39%
Elimination half-life = 31 h
Protein binding > 99.9%
Definition
ChEBI: A pyrimidine that is 5-(pyrimidin-2-yl}amino-2-methylbenzenesulfonamide substituted at position 4 by a (2,3-dimethylindazol-6-yl)(methyl)amino group. Used as its hydrochloride salt for treatment of kidney cancer.
Clinical Use
Tyrosine kinase inhibitor:
Treatment of metastatic renal cell carcinoma and soft
tissue sarcoma
Drug interactions
Potentially hazardous interactions with other drugs
Antibacterials: avoid with clarithromycin, rifampicin
and telithromycin.
Antifungals: avoid with itraconazole, ketoconazole
and voriconazole.
Antipsychotics: avoid with clozapine (increased risk
of agranulocytosis).
Antivirals: avoid with atazanavir, boceprevir,
indinavir, ritonavir and saquinavir.
Grapefruit juice: avoid concomitant administration.
Avoid concomitant use with other inhibitors or
inducers of CYP3A4. Dose alterations may be
required.
Metabolism
Metabolism primarily by CYP3A4, with minor
contributions from CYP1A2 and CYP2C8. The four
principle pazopanib metabolites account for only 6% of
the exposure in plasma. One of these metabolites inhibits
the proliferation of VEGF-stimulated human umbilical
vein endothelial cells with a similar potency to that
of pazopanib, the others are 10- to 20-fold less active.
Therefore, activity of pazopanib is mainly dependent on
parent pazopanib exposure.
Elimination is mostly via the faeces.
References
[1] RAKESH KUMAR. Pharmacokinetic-pharmacodynamic correlation from mouse to human with pazopanib, a multikinase angiogenesis inhibitor with potent antitumor and antiangiogenic activity.[J]. Molecular Cancer Therapeutics, 2007, 6 7: 2012-2021. DOI:
10.1158/1535-7163.mct-07-0193[2] K. PODAR. The Small-Molecule VEGF-Receptor Inhibitor Pazopanib (GW786034B) Targets Both Tumor and Endothelial Cells in Multiple Myeloma.[J]. Blood, 2006, 108 1: 5003-5003. DOI:
10.1182/blood.v108.11.5003.5003
