Capmatinib

Capmatinib (INCB-28060, INC-280) is a highly potent, selective, ATP competitive inhibitor of c-MET kinase with IC50 of 0.13 nM, displays no activity against RONβ, EGFR and HER-3; inhibits c-MET phosphorylation (IC50=1 nM) in SNU-5 human gastric cancer cell line, is slightly more potent in H596 and H1437 lung cancer cell lines that express mutant c-MET due to an exon 14 deletion and a R988C mutation; inhibits c-MET phosphorylation and tumor growth in c-MET-driven mouse tumor models.Lung Cancer Phase 3 Clinical (In Vitro) :Capmatinib (INCB28060) inhibits c-MET phosphorylation with an IC50 value of approximately 1 nM and a concentration of approximately 4 nM inhibits c-MET more than 90%, which is reversible and the effect is significantly reduced in several hours after the compound is removed and completely disappeared by 48 hours.Capmatinib (INCB28060) (0-10000 nM; 72 h) inhibits the proliferation of SNU-5, S114, H441 and U-87MG.Capmatinib (INCB28060) (0.06-62.25 nM; 2h) effectively inhibits phosphorylation of c-MET as well as c-MET pathway downstream effectors such as ERK1/2, AKT, FAK, GAB1, and STAT3/5.Capmatinib (INCB28060) (0.24-63 nM; over night) prevents HGF-stimulated H441 cell migration.Capmatinib (INCB28060) (0.5-50 nM; 20 min) suppresses phosphorylation of both EGFR and HER-3 rapidly.Capmatinib (INCB28060) (0-333 nM; 24 h) induces apoptosis in SNU-5 cells. (In Vivo) :Capmatinib (INCB28060) (1-30 mg/kg; PO, twice daily, for 2 weeks) exhibits dose-dependent inhibition of tumor growth, and shows well tolerance at all doses during the treatment periods, with no evidence of overt toxicity or weight loss in U-87MG tumor mice model.Capmatinib (INCB28060) (0.03-10 mg/kg; PO, single dosage) causes inhibition of c-MET phosphorylation in S114 tumor mice model.