E-7050

E-7050 (Golvatinib) is a potent, dual c-Met and VEGFR-2 tyrosine kinase inhibitor with IC50 of 14 and 16 nM (kinase phosphorylation inhibition) ; also strongly inhibits the growth of MKN45, EBC-1, Hs746T, and SNU-5 tumor cells with IC50 values of 37, 6.2, 23, and 24 nM, respectively, selectively inhibits the growth of the c-Met amplified tumor cell lines in vitro; specifically inhibits HGF and VEGF stimulated HUVEC growth with IC50 values of 17 nM and 84 nM respectively, but bFGF stimulated HUVEC; demonstrates inhibition of the phosphorylation of c-Met and VEGFR-2 in tumors, and strong inhibition of tumor growth and tumor angiogenesis in xenograft models.Liver Cancer Phase 2 Discontinued (In Vitro) :Golvatinib (E-7050) potently inhibits phosphorylation of both c-Met and VEGFR-2. Golvatinib also potently represses the growth of both c-met amplified tumor cells and endothelial cells stimulated with either HGF or VEGF.Golvatinib strongly inhibits the growth of MKN45, EBC-1, Hs746T, and SNU-5 tumor cells with IC50 values of 37, 6.2, 23, and 24 nM, respectively. The growth of A549, SNU-1 and 0MKN74 tumor cells is inhibited by Golvatinib with much higher IC50 values.Golvatinib circumvents resistance to all of the reversible, irreversible, and mutant-selective EGFR-TKIs induced by exogenous and/or endogenous HGF in EGFR mutant lung cancer cell lines, by blocking the Met/Gab1/PI3K/Akt pathway in vitro.Golvatinib also prevents the emergence of gefitinib-resistant HCC827 cells induced by continuous exposure to HGF. (In Vivo) :Golvatinib (E-7050) shows inhibition of the phosphorylation of c-Met and VEGFR-2 in tumors, and strong inhibition of tumor growth and tumor angiogenesis in xenograft models.Treatment of some tumor lines containing c-met amplifications with high doses of Golvatinib (50-200 mg/kg) induced tumor regression and disappearance. In a peritoneal dissemination model, Golvatinib shows an antitumor effect against peritoneal tumors as well as a significant prolongation of lifespan in treated mice.Golvatinib (E7050) plus Gefitinib results in marked regression of tumor growth associated with inhibition of Akt phosphorylation in cancer cells.