RAF709

RAF709 is a potent inhibitor of B-RAF and C-RAF (IC50s = 0.4 and 0.5 nM, respectively). It is selective for RAF kinases exhibiting >99% inhibition of only B-RAF, B-RAFV600E, and C-RAF in a panel of 456 kinases. However, DDR1, DDR2, FRK, and PDGFRbeta are also inhibited by >80% at a concentration of 1 µM. RAF709 inhibits phosphorylation of MEK and ERK (EC50s = 0.02 and 0.1 µM, respectively) with minimal paradoxical activation, stabilizes BRAF-CRAF dimers (EC50 = 0.8 µM), and reduces proliferation of Calu-6 RAS mutant cells (EC50 = 0.95 µM). In a Calu-6 mouse non-small cell lung cancer (NSCLC) xenograft model, RAF709 (10-200 mg/kg) reduces ERK phosphorylation and decreases tumor volume in a dose-dependent manner without affecting total body weight.Formal Name: N-[2-methyl-5'-(4-morpholinyl)-6'-[(tetrahydro-2H-pyran-4-yl)oxy][3,3'-bipyridin]-5-yl]-3-(trifluoromethyl)-benzamide. CAS Number: 1628838-42-5. Molecular Formula: C28H29F3N4O4. Formula Weight: 542.6. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 30 mg/ml, DMSO: 30 mg/ml, DMSO:PBS (pH 7.2) (1:2): 0.33 mg/ml, Ethanol: 10 mg/ml. lambdamax: 224, 272, 301 nm. SMILES: O=C(NC1=CN=C(C)C(C2=CC(N3CCOCC3)=C(OC4CCOCC4)N=C2)=C1)C5=CC(C(F)(F)F)=CC=C5. InChi Code: InChI=1S/C28H29F3N4O4/c1-18-24(15-22(17-32-18)34-26(36)19-3-2-4-21(13-19)28(29,30)31)20-14-25(35-7-11-38-12-8-35)27(33-16-20)39-23-5-9-37-10-6-23/h2-4,13-17,23H,5-12H2,1H3,(H,34,36). InChi Key: FYNMINFUAIDIFL-UHFFFAOYSA-N.