Mechanism of action: B-Raf serine/threonine-protein kinase (BRAF) and V600E mutation inhibitor

Preclinical pharmacology

AZ12419304 is a pan-RAF inhibitor that does not up-regulate MAPK signaling in WT BRAF cells. It binds BRAF WT and V600E with a potency of <80nM.  Its IC50 in cells is <100nM. The cell GI50in A375 cells containing V600E mutation is <250nM.

AZ12419304 showed tumour growth inhibition at 60mpk BID for 10 days.

Decreased pERK (PD) can be measured in tumours from 2-8 hours post treatment. pERK levels return to pre-dose levels by 16 hours.

Additional Information

Gene information from the NCBi

This compound works on the following genes: