Page 16 - 《中国药科大学学报》2025年第5期

学报
548 Journal of China Pharmaceutical University 2025, 56(5): 548 − 556

第二代蛋白精氨酸甲基转移酶 5 抑制剂的研究进展

胡浙棋 ，尹春香 ，毛慧欢，常艺清，朱启华，徐云根，龚国清 ，邹 毅 **
#
#
*
（中国药科大学药学院, 南京 211198）

摘 要 蛋白精氨酸甲基转移酶 5（PRMT5）在多种癌症中高表达，近年来已成为癌症治疗的重要靶标。然而，第一代
PRMT5 抑制剂缺乏选择性，导致显著的血液毒性，严重限制了其临床应用；第二代 PRMT5 抑制剂通过特异性靶向甲硫腺苷
磷酸化酶（MTAP）缺失的肿瘤细胞，而不影响正常细胞，从而显著提高了安全性和疗效。本文总结了 PRMT5 在 MTAP 缺
失肿瘤细胞中的生物学机制，系统回顾了当前处于临床研究阶段的五款第二代 PRMT5 抑制剂的研发历程、分子的结合模式
以及最新的临床试验进展，旨在为该领域的进一步研究提供参考。
关键词 蛋白精氨酸甲基转移酶 5；甲硫腺苷磷酸化酶；甲硫腺苷；合成致死
中图分类号 R914 文献标志码 A 文章编号 1000−5048(2025)05−0548−09
doi：10.11665/j.issn.1000−5048.2025021201

引用本文 胡浙棋，尹春香，毛慧欢，等. 第二代蛋白精氨酸甲基转移酶 5 抑制剂的研究进展 [J]. 中国药科大学学报，2025，56（5）：548 −
556.

Cite this article as: HU Zheqi, YIN Chunxiang, MAO Huihuan, et al. Research progress on second-generation protein arginine
methyltransferase 5 inhibitors[J]. J China Pharm Univ, 2025, 56(5): 548 − 556.

Research progress on second-generation protein arginine methyltransferase

5 inhibitors
*
#
#
HU Zheqi , YIN Chunxiang , MAO Huihuan, CHANG Yiqing, ZHU Qihua, XU Yungen, GONG Guoqing , ZOU Yi **
School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China
Abstract Protein arginine methyltransferase 5 (PRMT5) exhibits elevated expression levels in a variety of
cancers and has emerged as a critical target for cancer therapy in recent years. However, first-generation PRMT5
inhibitors have exhibited inadequate selectivity, leading to significant hematological toxicity, thus limiting their
clinical utility. The second-generation PRMT5 inhibitors have shown marked improvement in safety and efficacy
by selectively targeting MTAP-null tumor cells without impacting normal cells. This review systematically
summarizes the biological and functional roles of PRMT5 in MTAP-deficient tumor cells, and comprehensively
analyzes the research and development process, molecular binding mechanisms, and the latest advancements in
clinical trials of the five second-generation PRMT5 inhibitors currently under investigation, aiming to provide
valuable insights for further in-depth studies in this field.
Key words protein arginine methyltransferase 5; methioadenosine phosphorylase; methylthioadenosine;
synthetic lethal

This study was supported by the National Innovation and Entrepreneurship Training Program for Undergraduate (202510316012Z)

#
HU Zheqi and YIN Chunxiang contributed equally to this work

*
收稿日期 2025-02-12 通信作者 Tel：18021535796 E-mail：gonggq@hotmail.com
**
Tel：13260857396 E-mail：zouyi@cpu.edu.cn
基金项目 国家级大学生创新创业训练计划项目（202510316012Z）
胡浙棋和尹春香为共同第一作者
#