Pazopanib Hydrochloride

Description

The growth of solid tumors is dependent on angiogenesis, the process wherein new capillaries are formed from existing blood vessels. VEGF is one of the most important inducers of angiogenesis and expressed at high levels by most tumors. Hence, the inhibition of VEGF or its receptor signaling system is an attractive target for cancer therapeutics. The most studied and developed inhibitors are monoclonal antibodies that neutralize VEGF (e.g., bevacizumab), anti-VEGF ribozymes (e.g., angiozyme), and small-molecule VEGFR kinase inhibitors (e.g., sunitinib, sorafenib). Pazopanib is the latest VEGFR kinase inhibitor to reach the market. It is indicated for the oral treatment of advanced RCC. The biological functions of the VEGF family are mediated by activation of three structurally homologous tyrosine kinase receptors, VEGFR-1, VEGFR-2, and VEGFR3. In vitro, pazopanib inhibits VEGFR-1, VEGFR-2, and VEGFR-3 with IC50 values of 10, 30, and 47 nM, respectively. In addition, it inhibits several of the closely related tyrosine receptor kinases, including platelet-derived growth-factor receptor β(PDGFR-β), c-kit, and fibroblast growth factor receptor-1 (FGFR1) with IC₅₀ values of 84, 74, and 140 nM, respectively. In human umbilical vein endothelial cells (HUVEC), pazopanib inhibits VEGF-induced proliferation more potently than basic fibroblast growth factor (bFGF)-stimulated proliferation (IC₅₀ = 21 nM vs. 721 nM) and concentration-dependently inhibits VEGF-induced VEGFR-2 phosphorylation (IC₅₀ = 7 nM). It also potently inhibits angiogenesis in Matrigel plug and corneal micropocket assays.
The most common adverse events associated with pazopanib were diarrhea, hypertension, hair depigmentation, nausea, anorexia, and vomiting.

The Uses of Pazopanib Hydrochloride

Pazopanib Hydrochloride (GW786034, Votrient, Armala) 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.

What are the applications of Application

Pazopanib Hydrochloride is a multi-targeted inhibitor