az304

Description: AZ304 is a novel, potent and ATP-competitive dual inhibitor of wild type BRAF and V600E mutant BRAF as well as wild type CRAF with IC50s of 79 nM, 38 nM and 68 nM, respectively. AZ304 also has significant effect on other kinases, such as p38 (IC50, 6 nM), CSF1R (IC50, 35 nM), weak effect on MAP3K7 (IC50, 6400 nM) and CSK (IC50, 7050 nM). AZ304 exerted potent inhibitory effects on both wild type and V600E mutant forms of the serine/threonine-protein kinase BRAF, with IC50 values of 79?nM and 38?nM, respectively. By suppressing ERK phosphorylation, AZ304 effectively inhibited a panel of human cancer cell lines with different BRAF and RAS genetic statuses. In selected colorectal cancer cell lines, AZ304 significantly inhibited cell growth in vitro and in vivo, regardless of BRAF genetic status. In addition, the EGFR inhibitor Cetuximab enhanced the potency of AZ304 independently of BRAF mutational status.

References: Br J Cancer. 2018 May; 118(11):1453-1463.