S49076 - FGFR 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemES49076Cat. No.: HY-12965CAS No.: 1265965-22-7分式: CHNOS分量: 438.5作靶點(diǎn): FGFR; c-Met/HGFR作通路: Protein Tyrosine Kinase/RTK儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 31 mg/mL (70.70 mM)* mean

2、s soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.2805 mL 11.4025 mL 22.8050 mL5 mM 0.4561 mL 2.2805 mL 4.5610 mL10 mM 0.2281 mL 1.1403 mL 2.2805 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 S49076新穎效的MET, AXL/MER和FGFR1/2/3抑制劑， IC50值于20 nM

3、。IC50 & Target METD1246N METY1248C METD1246H METY1248D8 nM (IC50) 16 nM (IC50) 11 nM (IC50) 17 nM (IC50)METY1248H METM1268T MET FGFR11/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE1 nM (IC50) 1 nM (IC50) 1 nM (IC50) 18 nM (IC50)FGFR1V561M FGFR2 FGFR2N549H FGFR323 nM (IC50) 17 nM (IC50) 19 nM (IC50

4、) 15 nM (IC50)AXL MER7 nM (IC50) 2 nM (IC50)體外研究 S49076 potently blocks cellular phosphorylation of MET, AXL, and FGFRs and inhibits downstreamsignaling. S49076 inhibits the proliferation of MET- and FGFR2-dependent gastric cancer cells, blocks MET-driven migration of lung carcinoma cells, and inhib

5、its colony formation of hepatocarcinoma cells expressingFGFR1/2 and AXL. Total inhibition of MET phosphorylation is seen after 2 hours of incubation with 10 nMS49076 and an with an IC50 of 2 nM. S49076 inhibits MET phosphorylation on this site in GTL-16 gastriccarcinoma cells with an IC50 value of 3

6、 nM. The IC50 for AXL inhibition by S49076 is 56 nM. S49076 inhibitsAXL signaling via AKT with an IC50 of 33 nM 1.體內(nèi)研究 In tumor xenograft models, a good pharmacokinetic/pharmacodynamic relationship for MET and FGFR2inhibition following oral administration of S49076 is established and correlated well

7、 with impact on tumorgrowth. MET, AXL, and the FGFRs have all been implicated in resistance to VEGF/VEGFR inhibitors such asbevacizumab. Combination of S49076 with bevacizumab in colon carcinoma xenograft models leads to neartotal inhibition of tumor growth. S49076 alone caused tumor growth arrest i

8、n bevacizumab-resistant tumors1.PROTOCOLCell Assay 1 For GTL-16 and SNU-16 viability assays, cells are seeded in 96-well microplates at the appropriate density inmedia containing 10% FCS and supplemented 48 hours later with serial dilutions of S49076 in a final volumeof 150 L per well. After 96 hour

9、s (GTL-16) or 120 hours (SNU-16) incubation (corresponding to 4 doublingtimes), 15 L of a solution of 5 mg/mL MTT is added to each well and the plates are incubated for 4 hours at37C. The formazan metabolite is solubilized in SDS for SNU-16 and, following removal of the MTT solution,in DMSO for GTL-

10、16. Global cell viability is estimated by measurement of optical density at 540 nm 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice: Female balb/c and swiss nu/nu mice are used in the study. The hydrochloride salt of S49076 isAdministration

11、 1 administered orally to mice in 1% (w/v) hydroxyethylcellulose in ammonium acetate buffer pH 4.5 in a volumeof 200 L per 20 g body weight. The maximal tolerated dose of S49076 in these mice is determined to be100 mg/kg/d (5 days a week for at least 3 weeks). Bevacizumab is dissolved in PBS and adm

12、inisteredintraperitoneally in a volume of 200 L per 20 g body weight 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Nat Commun. 2019 Apr 18;10(1):18122/3 Master of Small Molecules 您邊的抑制劑師www.MedChemESee more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Burbridge MF, et al. S49076 is a novel kinase inhibitor of MET, AXL, and FGFR with strong preclinical activity alone and in associationwith bevacizumab. Mol Cancer Ther. 2013 Sep;12(9):1749-62.McePdfHeigh