Amgen 2112819

Amgen 2112819 is an experimental small molecule Pan-RAF inhibitor developed by Amgen. It targets all three isoforms of the RAF kinase family—A-RAF, B-RAF, and C-RAF—which are critical nodes in the MAPK/ERK signaling pathway. By inhibiting the entire RAF family, the compound aims to overcome the paradoxical activation of the MAPK pathway often observed with selective BRAF inhibitors in cells with wild-type BRAF or upstream mutations like NRAS. Preclinical research presented at the AACR in 2013 demonstrated its activity in melanoma cell lines harboring rare BRAF mutations (such as V600K, V600R, L597S, and G466K), where it effectively reduced pMEK levels and inhibited cell growth, particularly when used in combination with MEK inhibitors.