S49076 is a novel, potent inhibitor of MET, AXL/MER, and FGFR1/2/3, blocking cellular phosphorylation of MET, AXL, and FGFRs.

Mer:2 nM, Axl:7 nM, FGFR3:15 nM, MET:1 nM, FGFR2:17 nM

S49076 強效地阻斷 MET、AXL 和 FGFRs 的细胞磷酸化，并在体外和体内抑制下游信号传导。在细胞模型中，S49076 抑制依赖 MET 和 FGFR2 的胃癌细胞增殖，阻止 MET 驱动的肺癌细胞迁移，以及抑制表达 FGFR1/2 和 AXL 的肝癌细胞的集落形成。S49076 对表达 MET、AXL 或 FGFRs 的癌细胞的活性、移动性和三维集落形成均有抑制作用[1]。

S49076在经受MET和FGFR依赖的肿瘤异种移植物中展示出显著的抗肿瘤活性，并且在被良好容忍的剂量下效果显著。该化合物对肿瘤的分布高，其中3.125 mg/kg剂量的半衰期约为7小时，相比之下血液中的半衰期不足2小时。在6.25 mg/kg及以上剂量时，MET磷酸化抑制率在16小时后保持超过50%。S49076还在贝伐珠单抗抵抗模型中显示活性，并且与贝伐珠单抗联用完全抑制结肠癌异种移植物的生长[1]。

For GTL-16 and SNU-16 viability assays, cells are seeded in 96-well microplates at the appropriate density in media containing 10% FCS and supplemented 48 hours later with serial dilutions of S49076 in a final volume of 150 μL per well. After 96 hours (GTL-16) or 120 hours (SNU-16) incubation, 15 μL of a solution of 5 mg/mL MTT is added to each well and the plates are incubated for 4 hours at 37℃. The formazan metabolite is solubilized in SDS for SNU-16 and, following removal of the MTT solution, in DMSO for GTL-16. Global cell viability is estimated by measurement of optical density at 540 nm. (Only for Reference)