BI 882370

Description

BI-882370 is an orally bioavailable RAF inhibitor with IC₅₀ values of 0.8, 0.8, and 0.6 nM for B-RAF^V600E, wild-type B-RAF, and C-RAF in the DFG-out inactive conformation, respectively. It is selective for RAF over a panel of kinases, including LCK, KIT, Src, LYNA, LYNB, and PDGFR (IC₅₀s = 49, 415, 485, 750, 715, and 1,220 nM, respectively). It inhibits proliferation of human B-RAF-mutant melanoma cells when used at concentrations ranging from 1 to 10 nM. It reduces tumor growth in multiple B-RAF-mutant melanoma and colorectal carcinoma mouse xenograft models when administered at a dose of 25 mg/kg twice per day. BI-882370, alone and in combination with trametinib , induces tumor regression in an A375 melanoma mouse xenograft model with no resistance developing within three or five weeks, respectively.