Title:Research Progress on Small-molecule Inhibitors of Protein Arginine
Methyltransferase 5 (PRMT5) for Treating Cancer
Volume: 23
Issue: 21
Author(s): Chaohua Guo, Lintao Wu, Xumei Zheng, Lin Zhao, Xiaojia Hou, Zhijun Wang*Chun Han*
Affiliation:
- Department of Chemistry, Key Laboratory of Antitumor Drugs and Companion Diagnostic Reagents, Changzhi University,
Changzhi, 046011, Shanxi, China
- Department of Chemistry, Key Laboratory of Antitumor Drugs and Companion Diagnostic Reagents, Changzhi University,
Changzhi, 046011, Shanxi, China
Keywords:
PRMT5, Antitumor targets, Small-molecule inhibitors, Arginine methylation, PRMT5 enzyme activity, Drug research.
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.
