Drug discovery targeting protein arginine methyltransferase 5 (PRMT5): an update

Protein arginine methyltransferase 5 (PRMT5) plays an important role in regulating gene expression, cell differentiation and development, and chromatin structure by catalyzing the methylation of histones and non-histone proteins. The aberrant expression of PRMT5 is closely associated with the occurrence and progression of various diseases, particularly malignant tumors. Accordingly, developing potent and specific PRMT5 inhibitors may provide a potential novel therapeutic approach. In this Perspective, we highlight the structures, the biological functions, regulatory mechanisms, relevant signaling pathways, and associations with cancer development of PRMT5, as well as the recent advances in drug discovery strategies targeting PRMT5. The challenges, opportunities, and future directions for developing PRMT5 inhibitors and degraders are also discussed.