Description: S49076 is a novel, potent inhibitor of MET, AXL/MER, and FGFR1/2/3. S49076 potently blocked cellular phosphorylation of MET, AXL, and FGFRs and inhibited downstream signaling in vitro and in vivo. In cell models, S49076 inhibited the proliferation of MET- and FGFR2-dependent gastric cancer cells, blocked MET-driven migration of lung carcinoma cells, and inhibited colony formation of hepatocarcinoma cells expressing FGFR1/2 and AXL. In tumor xenograft models, a good pharmacokinetic/pharmacodynamic relationship for MET and FGFR2 inhibition following oral administration of S49076 was established and correlated well with impact on tumor growth. MET, AXL, and the FGFRs have all been implicated in resistance to VEGF/VEGFR inhibitors such as bevacizumab. A phase I study with S-49076 is currently underway in patients with advanced solid tumors. Mol Cancer Ther; 12(9); 1749-62.
Synonym: S-49076; S49076; S 49076.
IUPAC/Chemical Name: (Z)-3-((3-((4-(morpholinomethyl)-1H-pyrrol-2-yl)methylene)-2-oxoindolin-5-yl)methyl)thiazolidine-2,4-dione
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Chemical Formula: C22H22N4O4S
Exact Mass: 438.13618
Molecular Weight: 438.502
Elemental Analysis: C, 60.26; H, 5.06; N, 12.78; O, 14.59; S, 7.31
1: Burbridge MF, Bossard CJ, Saunier C, Fejes I, Bruno A, Léonce S, Ferry G, Da
Violante G, Bouzom F, Cattan V, Jacquet-Bescond A, Comoglio PM, Lockhart BP,
Boutin JA, Cordi A, Ortuno JC, Pierré A, Hickman JA, Cruzalegui FH, Depil S.
S49076 is a novel kinase inhibitor of MET, AXL, and FGFR with strong preclinical
activity alone and in association with bevacizumab. Mol Cancer Ther. 2013
Sep;12(9):1749-62. doi: 10.1158/1535-7163.MCT-13-0075. Epub 2013 Jun 26. PubMed