NVP-ACC789

NVP-ACC789 is an inhibitor of human VEGFR-1, VEGFR-2 (mouse VEGFR-2), VEGFR-3 and PDGFR-β with IC₅₀s of 0.38, 0.02 (0.23), 0.18, 1.4 μM, respectively. IC50 & Target: IC50: 0.38 μM (human VEGFR-1), 0.02 μM (human VEGFR-2), 0.23 μM (mouse VEGFR-2), 0.18 μM (human VEGFR-3), 1.4 μM (human PDGFR-β)^[1] In Vitro: The enzymatic kinase assays demonstrate that NVP-ACC789 is an inhibitor of human VEGFR-1, VEGFR-2 (mouse VEGFR-2), VEGFR-3 and PDGFR-β with IC₅₀s of 0.38, 0.02 (0.23), 0.18, 1.4 μM, respectively. In VEGF-treated cultures, addition of the VEGFR-2 inhibitor NVP-ACC789 reduces BME cell number to baseline levels from 1 μM. Likewise, bFGF-induced BME cell proliferation is reduced markedly by NVP-ACC789 from 1 to 10 μM, without however reaching basal levels. NVP-ACC789 is found to be a potent inhibitor of VEGF-induced HUVE cell proliferation with an IC₅₀ of 1.6 nM. NVP-ACC789 also completely inhibits VEGF-induced BME and BAE cell invasion and VEGF-C-induced BAE cell invasion. The inhibition is dose-dependent in both cell types with a maximal effect from 1 μM^[1]. In Vivo: NVP-ACC789 which is given in daily oral doses for 6 days blocks VEGF-induced angiogenesis in a dose-dependent manner. NVP-ACC789 also inhibits the response to bFGF to some extent, but the dose-response curve is not linear for NVP-ACC789^[1].