Golvatinib (E7050) Chemical Properties

Melting point:

187 - 190°C

Boiling point:

867.5±65.0 °C(Predicted)

Density 

1.408

storage temp. 

Refrigerator

solubility 

DMSO (Slightly), Methanol (Slightly)

form 

Solid

pka

12.91±0.70(Predicted)

color 

White to Off-White

CAS DataBase Reference

928037-13-2

Golvatinib (E7050) Usage And Synthesis

Description

Golvatinib (E7050) is a dual c-Met and VEGFR-2 inhibitor with IC50 of 14 nM and 16 nM, does not inhibit bFGF-stimulated HUVEC growth (up to 1000 nM). Phase 1/2.

In vitro

In vitro studies indicate that 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 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.

In vivo

In vivo studies using 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 E7050 (50–200 mg/kg) induces 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. In another xenograft model research, tumors produced by HGF-transfected Ma-1 (Ma-1/HGF) cells are more angiogenic than vector control tumors and shows resistance to ZD1839. E7050 alone inhibits angiogenesis and retards growth of Ma-1/HGF tumors. E7050 combined with ZD1839 induces marked regression of tumor growth.

Description

Golvatinib is an orally bioavailable dual inhibitor of the receptor tyrosine kinases c-Met and VEGF receptor 2 (VEGFR2), which are involved in tumor progression. Golvatinib inhibits autophosphorylation of c-Met in MKN45 cells and phosphorylation of VEGFR2 in human umbilical vein endothelial cells (HUVECs; IC₅₀s = 14 and 16 nM, respectively). It also inhibits proliferation of a variety of cancer cell lines and of HUVECs stimulated with hepatocyte growth factor (HGF) and VEGF but not bFGF (IC₅₀s = 17, 84, and >1,000 nM for HGF-, VEGF-, and bFGF-stimulated HUVECs, respectively). In nude mouse xenograft models using MKN45, Hs746T, SNU-5, or EBC-1 cancer cells, golvatinib (25-200 mg/kg, daily) dose-dependently reduces tumor volume, and it increases survival in the model using MKN45 cells.

Uses

E7050 is a dual c-Met and VEGFR-2 inhibitor with IC50 of 14 nM and 16 nM, respectively.

Uses

Golvatinib is a potent and orally available inhibitor of c-MET and VEGFR-2 that exhibits potential antitumor properties by suppressing the overexpression of these receptor tyrosine kinases.

Definition

ChEBI: Golvatinib is an aromatic ether.

target

c-Met

References

[1] nakagawa t, tohyama o, yamaguchi a, et al. e7050: a dual c-met and vegfr-2 tyrosine kinase inhibitor promotes tumor regression and prolongs survival in mouse xenograft models. cancer science, 2010, 101(1): 210-215.

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