RAF709

RAF709 is a potent, selective, and efficacious RAF inhibitor with IC₅₀s of 0.4 nM and 0.5 nM for BRAF and CRAF, respectively^[1]. Antitumor efficacy^[1]. IC50 & Target: IC50: 0.4 nM (BRAF), 0.5 nM (CRAF)^[1] In Vitro: RAF709 stabilizes BRAF-CRAF dimers with an EC₅₀ of 0.8 μM. In cellular assays, the dose-response of pMEK and pERK are measured in Calu-6 cells with EC₅₀=0.02 and 0.1 μM with minimal paradoxical activation and inhibition of proliferation with EC₅₀=0.95 μM^[1]. In Vivo: RAF709 proves to be soluble, kinase selective, and efficacious in a KRAS mutant xenograft model. RAF709 shows dose-proportional increases in plasma exposure and a corresponding dosedependent inhibition of pERK in Calu-6 tumors. Treatment with RAF709 results in dose-dependent antitumor activity with 10 mg/kg being subefficacious (%T/C=92%), 30 mg/kg results in measurable antitumor activity (%T/C=46%), and 200 mg/kg results in mean tumor regression of 92%, while the same high dose is not efficacious in the PC3, KRAS WT model^[1].