INCB28060 Dihydrochloride

Description

INCB28060 Dihydrochloride is a novel, ATP-competitive inhibitor of c-MET kinase with an IC50 with 0.13 nM.

Uses

INCB28060 dihydrochloride exhibits picomolar enzymatic potency and is highly specific for c-MET with more than 10, 000-fold selectivity over a large panel of human kinases. This inhibitor potently blocks c-MET phosphorylation and activation of its key downstream effectors in c-MET-dependent tumor cell lines. As a result, INCB 28060 potently inhibits c-MET-dependent tumor cell proliferation and migration and effectively induces apoptosis in vitro.

Mechanism of action

As an inhibitor of the MET tyrosine kinase receptor, Capmatinib Dihydrocholride is able to selectively bind to the MET tyrosine kinase receptor, including mutations caused by MET exon 14 skipping, and inhibit the growth of cancer cells.

Synthesis

Fragments 235 and 241 are combined by cyclization in hot ethylene glycol to generate imidazotriazine compound 242. Next, imidazotriazine compound 242 is hydrolyzed under acidic conditions in aqueous phase to obtain benzoic acid 243. Benzoic acid 243 then undergoes an amidation reaction, which involves reaction with an amine to form an amide bond. Finally, capmatinib hydrochloride is obtained by treatment with 6N hydrochloric acid.