Capmatinib (dihydrochloride)

Capmatinib (INC280; INCB28060) dihydrochloride is a potent, orally active, selective, and ATP competitive c-Met kinase inhibitor (IC₅₀=0.13 nM). Capmatinib dihydrochloride can inhibit phosphorylation of c-MET as well as c-MET pathway downstream effectors such as ERK1/2, AKT, FAK, GAB1, and STAT3/5. Capmatinib dihydrochloride potently inhibits c-MET-dependent tumor cell proliferation and migration and effectively induces apoptosis. Antitumor activity. Capmatinib dihydrochloride is largely metabolized by CYP3A4 and aldehyde oxidase^[1][2][3]. IC50 & Target:IC₅₀: 0.13 nM (c-MET)^[1] 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^[1].
Capmatinib (INCB28060) (0-10000 nM; 72 h) inhibits the proliferation of SNU-5, S114, H441 and U-87MG^[1].
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^[1].
Capmatinib (INCB28060) (0.24-63 nM; over night) prevents HGF-stimulated H441 cell migration^[1].
Capmatinib (INCB28060) (0.5-50 nM; 20 min) suppresses phosphorylation of both EGFR and HER-3 rapidly^[1].
Capmatinib (INCB28060) (0-333 nM; 24 h) induces apoptosis in SNU-5 cells^[1]. 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^[1].
Capmatinib (INCB28060) (0.03-10 mg/kg; PO, single dosage) causes inhibition of c-MET phosphorylation in S114 tumor mice model^[1].