CCT196969 是泛-Raf 抑制剂，抑制B-Raf、BRafV600E和CRaf，IC50分别为 0.1、0.04、和 0.01 μM。

CCT196969 is a novel orally available, pan-RAF inhibitor with anti-SRC activity. It also inhibits SRC, LCK, and the p38 MAPKs.

CCT196969 induces caspase 3 and PARP cleavage, thus induces apoptosis. CCT196969 does not drive paradoxical pathway activation and inhibit MEK/ERK in BRAF and NRAS mutant melanoma. CCT196969 is active against melanoma and colorectal cancer cell lines that are mutant for BRAF, but not cancer cells that are wild-type for BRAF and NRAS.

Oral dosing at 10 mg/kg/day of CCT196969 results in plasma concentrations ～1 μM at 24 hr. It is orally bioavailable at ～55%. CCT196969 is extremely well tolerated at the doses assessed and does not produce any significant adverse effects in vivo.

Cell lines: cell line derived from a vemurafenib-resistant melanoma. Method: The three cell lines derived from tumors displaying resistance to vemurafenib are incubated with DMSO (control),PLX4720,CCT196969,or CCT241161 (1 μM; 4 hr).Protein extracts are prepared in CLB1 lysis buffer,and samples are analyzed by Zeptosens RPPA(reverse phase protein arrays).

Animal Models: CD-1 mice. Formulation: 5% DMSO,95% water. Dosages: 20 mg/kg . Administration: oral gavage

1163719-56-9

C27H24FN7O3

513.533

DMSO:100 mg/mL (194.73 mM)
H2O:Insoluble
Ethanol:Insoluble
Powder: -20°C for 3 years
In solvent: -80°C for 2 years