Golvatinib (E7050)

Cas No.:	928037-13-2
Chemical Name:	Golvatinib
Synonyms:	E-7050;N-[2-Fluoro-4-[[2-[[[4-(4-methylpiperazin-1-yl)piperidin-1-yl]carbonyl]amino]pyridin-4-yl]oxy]phenyl]-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide;Golvatinib (E7050);1-N'-[2-fluoro-4-[2-[[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]amino]pyridin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide;E7050;Golvatinib;Golvatinib (USAN);UNII-516Z3YP58E;516Z3YP58E;N-(2-fluoro-4-(2-(4-(4-methylpiperazin-1-yl)piperidine-1-carboxamido)pyridin-4-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide;Golvatinib [USAN:INN];N-(2-Fluoro-4-{[2-({[4-(4-methylpiperazin-1-yl)piperidin-1-yl]carbonyl}amino)pyridin;Golvatinib tartrate;N-(2-Fluoro-4-{[2-({[4-(4-methylpiperazin-1-yl)piperidi;N-[2-Fluoro-4-[[2-[[[4-(4-methyl-1-piperazinyl)-1-piperidinyl]carbonyl]amino]-4-pyridinyl]oxy]phenyl]-N′-(4-fluorophenyl)-1,1-cyclopropanedicarboxamide (ACI);1-N′-[2-Fluoro-4-[2-[[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]amino]pyridin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide;E 7050;N-[2-Fluoro-4-[[2-[[[4-(4-methylpiperazin-1-yl)piperidin-1-yl]carbonyl]amino]pyridin-4-yl]oxy]phenyl]-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
SMILES:	O=C(N1CCC(N2CCN(C)CC2)CC1)NC1C=C(OC2C=C(F)C(NC(C3(CC3)C(NC3C=CC(F)=CC=3)=O)=O)=CC=2)C=CN=1
Formula:	C33H37F2N7O4
M.Wt:	633.688194036484
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	E-7050 is a potent dual inhibitor of both c-Met and VEGFR2 kinases with IC50s of 14 and 16 nM, respectively.
In Vivo:	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 E7050v (50–200 mg/kg) induced tumor regression and disappearance. In a peritoneal dissemination model, E7050 shows an antitumor effect against peritoneal tumors as well as a significant prolongation of lifespan in treated mice[1]. E7050 plus gefitinib results in marked regression of tumor growth associated with inhibition of Akt phosphorylation in cancer cells[2].
In Vitro:	E7050 potently inhibits phosphorylation of both c-Met and VEGFR-2. E7050 also potently represses the growth of both c-met amplified tumor cells and endothelial cells stimulated with either HGF or VEGF. E7050 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 E7050 with much higher IC50 values[1]. E7050 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. E7050 also prevents the emergence of gefitinib-resistant HCC827 cells induced by continuous exposure to HGF[2].
Cell Assay:	Cells (1000-3000 cells/100 μL/well) are seeded on 96-well culture plates with various concentrations of E7050 and cultured for 3 days. Then, 10 μL of WST-8 reagent is added to each well, and absorbance is measured at 450 nm compared with a reference measurement at 660 nm using a MTP-500 microplate reader[1].
Animal Administration:	Mice: Nude mice bearing MKN45, Hs746T, SNU-5, or EBC-1 tumors are administered E7050 (25, 50, 100, 200 mg/kg) or vehicle only as a control, once a day. Tumor volume is measured using calipers on the indicated days (0-15 days)[1].
References:	[1]. Nakagawa T et al. E7050: a dual c-Met and VEGFR-2 tyrosine kinase inhibitor promotes tumor regression and prolongs survival in mouse xenograft models. Cancer Sci, 2010, 101(1), 210-215. [2]. Wang W et al. Met kinase inhibitor E7050 reverses three different mechanisms of hepatocyte growth factor-induced tyrosine kinase inhibitor resistance in EGFR mutant lung cancer. Clin Cancer Res, 2012, 18(6), 1663-1671.