Nucleoside protein arginine methyltransferase 5 (PRMT5) inhibitors

Protein Arginine Methyltransferase 5 (PRMT5) is known to symmetrically dimethylate numerous cytosolic and nuclear proteins that are involved in a variety of cellular processes. Recent findings have revealed its potential as a cancer therapeutic target. PRMT5 selective inhibitors, GSK3326595, a substrate competitive inhibitor, and JNJ64619178, a SAM (S-adenosyl-l-methionine) mimetic/competitive inhibitor, have entered clinic trials for multiple cancer types. This review focuses on the recent developments in SAM mimetic nucleoside PRMT5 inhibitors, their SAR and structural insight based on published co-crystal structures.