Protein Arginine Methyltransferase 5 (PRMT5) as an Anticancer Target and Its Inhibitor Discovery

PRMT5 is a major enzyme responsible for symmetric dimethylation of arginine residues on both histone and non-histone proteins, regulating many biological pathways in mammalian cells. PRMT5 has been suggested as a therapeutic target in a variety of diseases including infectious disease, heart disease, and cancer. Many PRMT5 inhibitors have been discovered in the past 5 years, and one entered clinical trial in 2015 for the treatment of solid tumor and mantle cell lymphoma (MCL). The aim of this review is to summarize the current understanding of the roles of PRMT5 in cancer and the discovery of PRMT5 enzymatic inhibitors. By reviewing the structure–activity relationship (SAR) of known inhibitors of PRMT5, we hope to provide guidance for future drug designs and inhibitor optimization. Opportunities and limitations of PRMT5 inhibitors for the treatment of cancer are also discussed.