raf709

Description: RAF709 is a novel and potent inhibitor of the Raf kinase B/C isoforms (compound example 131 from patent WO2014151616A1) developed through a hypothesis-driven approach focusing on drug-like properties. It has IC50 values of 0.5 and 1.8 nM for c-Raf and b-Raf, respectively. It exhibited a high level of selectivity over other kinases and is soluble, kinase selective, and efficacious in a KRAS mutant xenograft model. RAF709 also demonstrated greater than 99% on-target binding to BRAF, BRAFV600E, and CRAF at 1 uM and negligible off-targets binding with DDR1 (> 99%), DDR2 (86%), FRK (92%), and PDGFRb (96%). RAF709 in combination with a MEK inhibitor provides enhanced antitumor activity in KRASmut tumors. Thereby it has the potential to be used for treating certain disorders associated with excessive Raf kinase activity, including cell proliferation disorders such as cancers.

References: Cancer Res. 2018; 78(6):1537-1548; J Med Chem. 2017; 60(12):4869-4881; WO2014151616A1