AMG-337 is an effective and highly specific ATP-competitive MET kinase inhibitor. In enzymatic assays, AMG-337(AMG337) inhibits MET kinase activity (IC50: < 5 nM).

MET kinase:< 5 nM

AMG 337有效抑制WT MET的酶活性及乳头状肾细胞癌中一部分MET突变体。AMG 337无法抑制Y1230和D1228突变体，这可能是因为MET激酶域激活回路非活性构型被破坏所致。此外，AMG 337还能抑制基于细胞的HGF诱导的PC3细胞中MET磷酸化，IC50为5 nM。AMG 337抑制MET依赖的癌细胞系增殖，并在MET扩增的胃癌细胞系中抑制通过PI3K和MAPK途径的信号传导，从而显著影响细胞增殖与生存[1]。

AMG 337显示出卓越的效力，在0.75 mg/kg (32 nmol/L自由化合物浓度)的剂量下对Gab-1磷酸化的抑制率超过90%。AMG 337在与完全MET抑制相对应的持续给药剂量下良好耐受，连续24小时，表明AMG 337具备测试MET在人类癌症中作用所需的临床前属性[1]。

To evaluate the effect of AMG 337 on viability, cells are seeded in 96-well plates at an optimal density to ensure proliferation throughout the duration of the experiments. Cells are treated for 72 hours with a 10-point, 3-fold, serial dilution of AMG 337 using a top concentration of 3 mmol/L. Viability is measured with the CellTiter-Glo Luminescent Cell Viability Assay.(Only for Reference)