Vatalanib (dihydrochloride)

Vatalanib dihydrochloride (PTK787 dihydrochloride) is a BBB-permeable VEGFR2/KDR inhibitor with an IC₅₀ of 37 nM. IC50 & Target:IC50: 37 nM (VEGFR2/KDR)^[1] In Vitro:Vatalanib also inhibits Flk, c-Kit and PDGFRβ with IC₅₀ of 270 nM, 730 nM and 580 nM, respectively. Vatalanib shows the anti-proliferation effect by inhibiting thymidine incorporation induced by VEGF in HUVECs with and IC₅₀ of 7.1 nM, and dose-dependently suppresses VEGF-induced survival and migration of endothelial cells in the same dose range without cytotoxic or antiproliferative effect on cells that do not express VEGF receptors^[1]. A recent study shows that Vatalanib significantly inhibits the growth of hepatocellular carcinoma cells and enhances the IFN/5-FU induced apoptosis by increasing proteins levels of Bax and reduced Bcl-xL and Bcl-2^[2]. In Vivo:Vatalanib induces dose-dependent inhibition of the angiogenic response to VEGF and PDGF in both a growth factor implant model and a tumor cell-driven angiogenesis model after once-daily oral dosing (25-100 mg/kg). In the same dose range, Vatalanib also inhibits the growth and metastasesof several human carcinomas in nude mice without significant effect on circulating blood cells or bone marrow leukocytes^[1].