Glumetinib is a potent inhibitor of c-Met (IC50 = 0.42 nM).1 It is greater than 2,400-fold selective for c-Met over a panel of 312 kinases. Glumetinib (0.001-1 μM) inhibits c-Met phosphorylation in and proliferation of MET-overexpressing EBC-1 lung and MKN45 gastric cancer cells. It inhibits NCI H441 cell motility and invasion induced by hepatocyte growth factor (HGF) when used at a concentration of 10 nM. Glumetinib (2.5-10 mg/kg) reduces tumor volume in MKN45, SNU-5, and EBC-1 mouse xenograft models. It also reduces tumor growth in MET amplification-containing non-small cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC) patient-derived xenograft (PDX) mouse models.
1.Ai, J., Chen, Y., Peng, X., et al.Preclinical evaluation of SCC244 (glumetinib), a novel, potent, and highly selective inhibitor of c-Met in MET-dependent cancer modelsMol. Cancer Ther.17(4)751-762(2017)