tcsc0103 Tivozanib

Tivozanib (AV-951; KRN951) is a highly potent and selective VEGFR 1/2/3 inhibitor with IC₅₀s of 0.21, 0.16, and 0.24 nM in cell assay, respectively.

IC50 & Target: IC50: 0.21 nM (VEGFR 1), 0.16 nM (VEGFR 2), 0.24 nM (VEGFR 3)^[1]

In Vitro: Tivozanib potently inhibits VEGF-induced VEGFR2 phosphorylation in endothelial cells (IC₅₀=0.16 nM). It also inhibits ligand-induced phosphorylation of PDGFRβ and c-Kit (IC₅₀=1.72 and 1.63 nM, respectively). Tivozanib blocks VEGF-dependent, but not VEGF-independent, activation of mitogenactivated protein kinases and proliferation of endothelial cells. It inhibits VEGF-mediated migration of human umbilical vein endothelial cells^[1].

In Vivo: Following p.o. administration to athymic rats, Tivozanib decreases the microvessel density within tumor xenografts and attenuates VEGFR-2 phosphorylation levels in tumor endothelium. It also displays antitumor activity against a wide variety of human tumor xenografts, including lung, breast, colon, ovarian, pancreas, and prostate cancer^[1].