PHA-665752-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEPHA-665752Cat. No.: HY-11107CAS No.: 477575-56-7分式: CHClNOS分量: 641.61作靶点: c-Met/HGFR; Autophagy作通路: Protein Tyrosine Kinase/RTK; Autophagy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

2、mg/mL (77.93 mM; Need ultrasonic)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (3.90 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (3.90 mM); Clear solution1/3 Master of Small Molecules 您边的抑制剂师www.MedChemEBIOLOGICAL ACTIVITY物活性 PHA-665752种有效、选择性的，ATP 竞争性的

3、 c-Met 激酶抑制剂，IC50 值为 9 nM。有作为靶向 c-Met治疗类癌症药物的潜 1。IC50 & Target IC50: 9 nM (c-Met) 1体外研究PHA-665752 is a potent and ATP-competitive inhibitor of c-Met kinase activity with a Ki of 4 nM and an IC50of 9 nM 1.PHA-665752 exhibits 50-fold selectivity for c-Met enzyme compared with the majority of kinases e

4、valuated1.PHA-665752 shows potent inhibition of c-Met RTK autophosphorylation in NIH3T3 cells engineered toexpress high levels of c-Met and hepatocyte growth factor (HGF) 1.PHA-665752 inhibits HGF-stimulated or constitutive phosphorylation of mediators of downstream of c-Metsuch as Gab-1, ERK, Akt,

5、STAT3, PLC-, and FAK in multiple tumor cell lines 1.PHA-665752 (0-1.25 M; 18 hours) potently inhibits HGF and c-Met-driven phenotypes such as cell growth(proliferation and survival), cell motility, invasion, and/or morphology of a variety of tumor cells 1.PHA-665752 (0-1.25 M; 72 hours) induces apop

6、tosis in both the presence and absence of HGF atconcentrations that inhibited tyrosine phosphorylation of c-Met in GTL-16 cells 1.PHA-665752 (0.0125-0.2 M; 4 hours) potent inhibits HGF-induced c-Met phosphorylation in A549 cells 1.Cell Proliferation Assay 1Cell Line: S114 cells, GTL-16 cells, NCI-H4

7、41 cells, or BxPC-3 cellsConcentration: 0 M, 0.002 M, 0.01 M, 0.05 M, 0.25 M, 1.25 MIncubation Time: 18 hoursResult: Potently inhibited HGF and c-Met-driven cell growth.Apoptosis Analysis 1Cell Line: GTL-16 cellsConcentration: 0 M, 0.002 M, 0.01 M, 0.05 M, 0.25 M, 1.25 MIncubation Time: 72 hoursResu

8、lt: Induced apoptosis in both the presence and absence of HGF at concentrations thatinhibited tyrosine phosphorylation of c-Met in GTL-16 cells. Immunoblot Analysis.Western Blot Analysis 1Cell Line: A549 cellsConcentration: 0.0125 M, 0.025 M,0.05 M,0.1 M,0.2 M2/3 Master of Small Molecules 您边的抑制剂师www

9、.MedChemEIncubation Time: 4 hoursResult: Potent inhibited HGF-induced c-Met phosphorylation in A549 cells.体内研究 PHA-665752 (7.5-30 mg/kg/day; i.v. ; for 9 days) exhibits statistically significant dose-dependent tumorgrowth inhibition of 68%, 39%, and 20% of vehicle control at the 30 mg/kg/day, 15 mg/

10、kg/day, and 7.5mg/kg/day doses, respectively 1.PHA-665752 shows a potent cytoreductive activity in a gastric carcinoma xenograft model 1.Animal Model: Female athymic mice (nu/nu, 812 weeks) bearing S114 or GTL-16 tumor xenografts 1Dosage: 7.5 mg/kg/day, 15 mg/kg/day, 30 mg/kg/dayAdministration: Intr

11、avenous injection; for 9 daysResult: Demonstrated statistically significant dose-dependent tumor growth inhibition.户使本产品发表的科研献 Int J Cancer. 2019 Jan 29. Mol Cancer Ther. 2018 Mar;17(3):603-613. Oncotarget. 2017 Jun 13;8(24):38717-38730. Harvard Medical School LINCS LIBRARYSee more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Christensen JG, et al. A selective small molecule inhibitor of c-Met kinase inhibits c-Met-dependent phenotypes in vitro and exhibitscytoreductive antitumor activity in vivo. Cancer Res. 2003 Nov 1;63(21):7345-55.McePdfHeightCaution: Pro