Research Progress on Small-molecule Inhibitors of Protein ArginineMethyltransferase 5 (PRMT5) for Treating Cancer

作者：Guo Chaohua, Lintao Wu, Xumei Zheng, Lin Zhao, Xiaojia Hou, Zhijun Wang, Chun Han · 发表于：Current Topics in Medicinal Chemistry · 年份：2023 · DOI：10.2174/1568026623666230712120527 · 被引用次数：8 · 研究领域：Cancer-related gene regulation、Machine Learning in Bioinformatics、Nuclear Receptors and Signaling

BACKGROUND: The protein arginine methyltransferase family includes nine members, with PRMT5 being the major type II arginine methyltransferase. PRMT5 is upregulated in a variety of tumors and promotes tumorigenesis and tumor cell proliferation and metastasis, making it a potential tumor therapy target. Recently, PRMT5 inhibitor research and development have become hotspots in the tumor therapy field. METHODS: We classified and summarized PRMT5 inhibitors according to different binding mechanisms. We mainly analyzed the structure, biological activity, and binding interactions of PRMT5 inhibitors with the PRMT5 enzyme. RESULTS: At present, many PRMT5 inhibitors with various mechanisms of action have been reported, including substrate-competitive inhibitors, SAM-competitive inhibitors, dual substrate-/SAMcompetitive inhibitors, allosteric inhibitors, PRMT5 degraders, MTA-cooperative PRMT5 inhibitors and PPI inhibitors. CONCLUSION: These inhibitors are beneficial to the treatment of tumors. Some drugs are being used in clinical trials. PRMT5 inhibitors have broad application prospects in tumor therapy.