928037-13-2 Usage
Description
Golvatinib (E7050) is a dual c-Met and VEGFR-2 inhibitor with IC50 of 14 nM and 16 nM, respectively. It is an orally bioavailable compound that targets the receptor tyrosine kinases c-Met and VEGF receptor 2 (VEGFR2), which play a role in tumor progression. Golvatinib inhibits autophosphorylation of c-Met in MKN45 cells and phosphorylation of VEGFR2 in human umbilical vein endothelial cells (HUVECs). It also suppresses the proliferation of various cancer cell lines and HUVECs stimulated with hepatocyte growth factor (HGF) and VEGF, but not bFGF.
Uses
Used in Oncology:
Golvatinib (E7050) is used as an antitumor agent for its potential to suppress the overexpression of c-Met and VEGFR-2 receptor tyrosine kinases. This suppression helps in inhibiting tumor progression and reducing tumor volume in various cancer types. In nude mouse xenograft models, golvatinib has been shown to dose-dependently reduce tumor volume and increase survival in certain cancer cell lines.
Used in Cancer Cell Line Proliferation Inhibition:
Golvatininib (E7050) is used as an inhibitor of cancer cell line proliferation, particularly for cell lines stimulated with hepatocyte growth factor (HGF) and VEGF. Its ability to inhibit the autophosphorylation of c-Met and phosphorylation of VEGFR2 contributes to the reduction of cancer cell growth.
Used in Angiogenesis Inhibition:
Golvatinib (E7050) is used as an inhibitor of angiogenesis, the process through which new blood vessels form from pre-existing vessels. By targeting VEGFR2, it can potentially limit the formation of new blood vessels that supply nutrients to tumors, thereby restricting their growth and spread.
Used in Preclinical Cancer Research:
Golvatinib (E7050) is used as a research tool in preclinical cancer studies to investigate the role of c-Met and VEGFR-2 in tumor progression and to explore the compound's potential as a therapeutic agent for various types of cancer.
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.
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.
Check Digit Verification of cas no
The CAS Registry Mumber 928037-13-2 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 9,2,8,0,3 and 7 respectively; the second part has 2 digits, 1 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 928037-13:
(8*9)+(7*2)+(6*8)+(5*0)+(4*3)+(3*7)+(2*1)+(1*3)=172
172 % 10 = 2
So 928037-13-2 is a valid CAS Registry Number.
