BI-882370

BI-882370 is an orally bioavailable RAF inhibitor with IC50 values of 0.8, 0.8, and 0.6 nM for B-RAFV600E, 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 (Cay-16292), induces tumor regression in an A375 melanoma mouse xenograft model with no resistance developing within three or five weeks, respectively.Formal Name: N-[3-[5-[(1-ethyl-4-piperidinyl)methylamino]-3-(5-pyrimidinyl)-1H-pyrrolo[3,2-b]pyridin-1-yl]-2,4-difluorophenyl]-1-propanesulfonamide. CAS Number: 1392429-79-6. Molecular Formula: C28H33F2N7O2S. Formula Weight: 569.7. Purity: >95%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 100µg/ml, DMSO: 100µg/ml, Ethanol: 100µg/ml. lambdamax: 235, 273, 350 nm. SMILES: CCN1CCC(N(C)C2=CC=C(N(C3=C(F)C=CC(NS(CCC)(=O)=O)=C3F)C=C4C5=CN=CN=C5)C4=N2)CC1. InChi Code: InChI=1S/C28H33F2N7O2S/c1-4-14-40(38,39)34-23-7-6-22(29)28(26(23)30)37-17-21(19-15-31-18-32-16-19)27-24(37)8-9-25(33-27)35(3)20-10-12-36(5-2)13-11-20/h6-9,15-18,20,34H,4-5,10-14H2,1-3H3. InChi Key: AEJACXAFHXBVHF-UHFFFAOYSA-N.