S49076

Biological Activity

S49076 is a novel and potent inhibitor of Met (c-Met), AXL/MER and FGFR1/2/3 with IC50 below 20 nM.

in vivo

S49076 effectively inhibits the phosphorylation of MET, AXL and FGFRs in cells, and inhibits their downstream signaling pathways in vitro and in vivo. In cellular models, it inhibits MET and FGFR2-dependent gastric cancer cells, prevents MET-driven migration of lung cancer cells, and inhibits colony formation of liver cancer cells expressing FGFR1/2 and AXL. S49076 inhibits cell viability, motile, three-dimensional colony formation of cancer cells expressing MET, AXL or FGFRs.

in vivo

S49076 has significant antitumor activity in MET- and FGFR-dependent tumor grafts. It is highly distributed in tumors, with a half-life of approximately 7 hours in tumors and less than 2 hours in blood at a dose of 3.125 mg/kg. At doses above 6.25 mg/kg, more than 50% of MET phosphorylation was inhibited for 16 hours. S49076 was also active in a bevacizumab-resistant model, and in combination with bevacizumab, completely inhibited the growth of colon cancer xenografts.

target

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(Cell-free assay)

Target	Value
Met (Cell-free assay)	1 nM
Mer (Cell-free assay)	2 nM
7 nM
FGFR3 (Cell-free assay)	15 nM
FGFR2 (Cell-free assay)	17 nM