Golvatinib-E-7050-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEGolvatinibCat. No.: HY-13068CAS No.: 928037-13-2Synonyms: E-7050分式: CHFNO分量: 633.69作靶点: c-Met/HGFR; VEGFR作通路: Protein Tyrosine Kinase/RTK储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 50 m

2、g/mL (78.90 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 1.5781 mL 7.8903 mL 15.7806 mL5 mM 0.3156 mL 1.5781 mL 3.1561 mL10 mM 0.1578 mL 0.7890 mL 1.5781 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配

3、，当天使；澄的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 3 mg/mL (4.73 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 3 mg/mL (4.73 mM); Clear solution3. 请依序添加每种溶剂： 10% DMSO 90% corn oil1/3 Master of Small

4、 Molecules 您边的抑制剂师www.MedChemESolubility: 3 mg/mL (4.73 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Golvatinib (E7050)c-Met 和 VEGFR2 的双重 抑制剂，IC50值分别为14 和 16 nM。IC50 & Target VEGFR2 c-Met16 nM (IC50) 14 nM (IC50)体外研究 Golvatinib (E7050) potently inhibits phosphorylation of both c-Met and VEGFR-2. Golvat

5、inib also potentlyrepresses the growth of both c-met amplified tumor cells and endothelial cells stimulated with either HGF orVEGF. Golvatinib strongly inhibits the growth of MKN45, EBC-1, Hs746T, and SNU-5 tumor cells with IC50values of 37, 6.2, 23, and 24 nM, respectively. The growth of A549, SNU-

6、1 and 0MKN74 tumor cells isinhibited by Golvatinib with much higher IC50 values 1. Golvatinib circumvents resistance to all of thereversible, irreversible, and mutant-selective EGFR-TKIs induced by exogenous and/or endogenous HGF inEGFR mutant lung cancer cell lines, by blocking the Met/Gab1/PI3K/Ak

7、t pathway in vitro. Golvatinib alsoprevents the emergence of gefitinib-resistant HCC827 cells induced by continuous exposure to HGF 2.体内研究 Golvatinib (E7050) shows inhibition of the phosphorylation of c-Met and VEGFR-2 in tumors, and stronginhibition of tumor growth and tumor angiogenesis in xenogra

8、ft models. Treatment of some tumor linescontaining c-met amplifications with high doses of Golvatinib (50-200 mg/kg) induced tumor regression anddisappearance. In a peritoneal dissemination model, Golvatinib shows an antitumor effect against peritonealtumors as well as a significant prolongation of

9、lifespan in treated mice 1. Golvatinib (E7050) plus Gefitinibresults in marked regression of tumor growth associated with inhibition of Akt phosphorylation in cancer cells2.PROTOCOLCell Assay 1 Cells (1000-3000 cells/100 L/well) are seeded on 96-well culture plates with various concentrations ofGolv

10、atinib and cultured for 3 days. Then, 10 L of WST-8 reagent is added to each well, and absorbance ismeasured at 450 nm compared with a reference measurement at 660 nm using a MTP-500 microplatereader 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Ani

11、mal Mice: Nude mice bearing MKN45, Hs746T, SNU-5, or EBC-1 tumors are administered Golvatinib (25, 50,Administration 1 100, 200 mg/kg) or vehicle only as a control, once a day. Tumor volume is measured using calipers on theindicated days (0-15 days) 1.MCE has not independently confirmed the accuracy

12、 of these methods. They are for reference only.户使本产品发表的科研献 Science. 2017 Dec 1;358(6367).2/3 Master of Small Molecules 您边的抑制剂师www.MedChemE Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. PLoS Biol. 2019 Apr 30;17(4):e3000229. Technical University of Munich. 24.01.2018.See more customer validatio

13、ns on HYPERLINK / www.MedChemEREFERENCES1. Nakagawa T et al. E7050: a dual c-Met and VEGFR-2 tyrosine kinase inhibitor promotes tumor regression and prolongs survival inmouse 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 kinaseinhibitor resistance in EGFR mutant lung cancer. Clin Cancer Res, 2012, 18(6), 1663-1671.