Golvatinib

928037-13-2

C33H37F2N7O4

DMSO : 50 mg/mL (78.90 mM; Need ultrasonic)

Protein Tyrosine Kinase/RTK; Protein Tyrosine Kinase/RTK

Golvatinib (E-7050) is a potent dual inhibitor of both c-Met and VEGFR2 kinases with IC₅₀s of 14 and 16 nM, respectively. IC50 & Target: IC50: 14 nM (c-Met), 16 nM (VEGFR2)^[1] In Vitro: Golvatinib (E7050) 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^[1]. 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^[2]. In Vivo: Golvatinib (E7050) 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^[1]. Golvatinib (E7050) plus Gefitinib results in marked regression of tumor growth associated with inhibition of Akt phosphorylation in cancer cells^[2].