AZ304

AZ304 is an ATP-competitive dual BRAF kinase inhibitor, potently inhibits wild type BRAF, V600E mutant BRAF and 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). Anti-tumor activity^[1]. IC50 & Target: IC50: 79 nM (BRAF^WT), 38 nM (BRAF^V600E), 68 nM (CRAF^WT), 6 nM (p38), 35 nM (CSF1R), 6400 nM (MAP3K7), 7050 nM (CSK)^[1] In Vitro: AZ304 (1 nM-100 μM) potently reduces ERK phosphorylation (p-ERK), with a mean EC₅₀ of 65 nM in the V600E mutant BRAF containing melanoma cell line A375, and EC₅₀s of 52 nM, 60 nM in the wild type BRAF melanoma cell line SK-MEL-31 with and without EGF^[1]. AZ304 also potently inhibits p-p38 in both BRAF genetic statuses cell lines^[1].
AZ304 (0, 0.1, 1, 10, 100 μM, 48 and 72 hours) dose-dependently inhibits the growth of RKO, HT-29, DiFi, and Caco-2, with GI₅₀s of 4.539 μM, 3.896 μM, 4.987 μM, 1.763 μM (48 hours) and 0.5032 μM, 0.3887 μM, 0.6354 μM, 0.3772 μM (72 hours), respectively^[1].
AZ304 (2 μM, 36 and 48 hours) decreases BRAF, p-ERK, p-AKT and p-mTOR levels, increases p-EGFR in both BRAF V600E mutant and BRAF wild type cells. AZ304 down-regulates p-EGFR, inhibits p-ERK, more potently suppresses BRAF, ERK, AKT and mTOR signalling pathways in combination with C225^[1].