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Current Topics in Medicinal Chemistry

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ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

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Review Article

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

Author(s): Chaohua Guo, Lintao Wu, Xumei Zheng, Lin Zhao, Xiaojia Hou, Zhijun Wang* and Chun Han*

Volume 23, Issue 21, 2023

Published on: 19 July, 2023

Page: [2048 - 2074] Pages: 27

DOI: 10.2174/1568026623666230712120527

Price: $65

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Abstract

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.

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