anvumetostat

Anvumetostat, also known as AMG 193, is an orally available small molecule that acts as a potent, selective, and MTA-cooperative protein arginine methyltransferase 5 (PRMT5) inhibitor. Developed by Amgen, it is designed to target cancers with methylthioadenosine phosphorylase (MTAP) deletion. MTAP deletion leads to the accumulation of methylthioadenosine (MTA), which sensitizes these cancer cells to PRMT5 inhibition. Anvumetostat selectively binds to PRMT5 in the presence of MTA, inhibiting its methyltransferase activity. This leads to decreased levels of monomethylated and dimethylated arginine residues in histones H2A, H3, and H4, modulating gene expression, inducing DNA damage, cell cycle arrest, and aberrant mRNA splicing, ultimately resulting in cell death in MTAP-deleted tumor cells while sparing normal cells. It is currently in clinical trials for various advanced MTAP-deleted solid tumors.

Other names

MTA Cooperative PRMT5 inhibitor