S49076 is a novel and potent inhibitor of MET/MET mutations, AXL/MER, and FGFR1/2/3 with IC50 values of 1nM/1-17nM, 7nM/2nM, 18nM/17nM/15nM, respectively. S49076 potently blocked cellular phosphorylation of MET (3-10nM), AXL (10-1000nM), and FGFRs (>300nM) and inhibited downstream signaling p-FRS2 and p-ERK in vitro. S49076 inhibited viability (IC50 values were 3, 167, and >10μM for GTL-16, SNU-16, and MKN-7, respectively), motility (IC50 for inhibition of HGF-induced cell motility of 14nM in A549 cells), and three-dimensional colony formation of cancer cells expressing MET, AXL, or FGFRs. Orally administered S49076 at doses ranging in 0.78-12.5mg/kg inhibited MET signaling in subcutaneous xenografts in balb/c nu/nu mice at doses, suggesting its good pharmacodynamics. Oral administration of S49076 inhibited tumor growth in mice xenograft GTL-16, U87-MG and SNU-16 at doses ranging in 3.125-50mg/kg, 6.25-50mg/kg and 37.5-100mg/kg, respectively[2].
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