AZ304 is a dual inhibitor of BRAF that effectively inhibits wild-type BRAF, mutant BRAF (V600E) and wild-type CRAF with IC50 values of 79 nM, 38 nM and 68 nM, respectively. AZ304 significantly inhibits other kinases, such as p38 (IC50, 6 nM), CSF1R (IC50, 35 nM). Has anti-tumor activity.
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].
Reference:
[1]. Ma R, et al. AZ304, a novel dual BRAF inhibitor, exerts anti-tumour effects in colorectal cancer independently of BRAF genetic status. Br J Cancer. 2018 May;118(11):1453-1463.