Vatalanib (succinate)

Vatalanib (PTK787) succinate is a potent and orally active VEGFR inhibitor with IC₅₀s of 37 nM, 77 nM, 270 nM, 660 nM, 730 nM, 1400 nM, and 580 nM for KDR, Flt-1, Flk, Flt-4, c-Kit, c-Fms, and PDGFR-β, respectively^[1]. In Vitro:Vatalanib (PTK787) inhibits VEGF-induced autophosphorylation of kinase insert domain-containing receptor (KDR), endothelial cell proliferation, migration, and survival in the nanomolar range in cell-based assays. In concentrations up to 1 µM, Vatalanib (PTK787) does not have any cytotoxic or antiproliferative effect on cells that do not express VEGF receptors^[1]. In Vivo:After oral dosing (50 mg/kg) to mice, plasma concentrations of Vatalanib (PTK787) remain above 1 μM for more than 8 h. Vatalanib (PTK787) induces dose-dependent inhibition of VEGF and PDGF-induced angiogenesis in a growth factor implant model, as well as a tumor cell-driven angiogenesis model after once-daily oral dosing (25-100 mg/kg)^[1].