CCT196969

CCT196969 is a pan-Raf inhibitor, which inhibits B-Raf, BRaf^V600E and CRAF with IC₅₀s of 0.1, 0.04, and 0.01 μM, respectively. IC50 & Target: IC50: 0.1 μM (B-Raf)^[1] In Vitro: CCT196969 is a pan-Raf inhibitor with anti-SRC activity. CCT196969 is an orally available, well-tolerated B-Raf inhibitor that directly inhibits B-Raf^V600E in cells. CCT196969 inhibits B-Raf at 100 nM and B-Raf^V600E at 40 nM. It inhibits CRaf at 12 nM, SRC at 26 nM, and LCK at 14 nM. CCT196969 is active against melanoma and colorectal cancer cell lines that are mutant for B-Raf. CCT196969 induces caspase 3 and PARP cleavage, demonstrating that it induces apoptosis^[1]. In Vivo: CCT196969 is extremely well tolerated and does not produce any significant adverse effects in vivo. It inhibits the growth of NRAS mutant DO4 tumor xenografts in nude mice. CCT196969 inhibits ERK and SRC and induce tumor regression in a PDX from the resistant tumor without causing body weight loss in the mice^[1].