靶向蛋白精氨酸甲基转移酶5 （PRMT5）的药物发现：最新进展

IF 3.3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic & Medicinal Chemistry Pub Date : 2025-05-20 DOI:10.1016/j.bmc.2025.118240

Zhouyang Gu , Weizheng Kong , Xing Liu , Liangju Hu , Yucheng Zhou , Zhenchu Liang , Minyue Zhang , Dongyin Chen , Fei Li , Weilin Chen

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引用次数: 0

摘要

蛋白精氨酸甲基转移酶5 （Protein arginine methyltransferase 5, PRMT5）通过催化组蛋白和非组蛋白的甲基化，在基因表达、细胞分化发育和染色质结构调控中发挥重要作用。PRMT5的异常表达与各种疾病特别是恶性肿瘤的发生和发展密切相关。因此，开发有效和特异性的PRMT5抑制剂可能提供潜在的新治疗方法。本文将重点介绍PRMT5的结构、生物学功能、调控机制、相关信号通路及其与癌症发展的关系，以及针对PRMT5的药物发现策略的最新进展。讨论了开发PRMT5抑制剂和降解剂的挑战、机遇和未来发展方向。

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Drug discovery targeting protein arginine methyltransferase 5 (PRMT5): an update

Protein arginine methyltransferase 5 (PRMT5) plays an important role in regulating gene expression, cell differentiation and development, and chromatin structure by catalyzing the methylation of histones and non-histone proteins. The aberrant expression of PRMT5 is closely associated with the occurrence and progression of various diseases, particularly malignant tumors. Accordingly, developing potent and specific PRMT5 inhibitors may provide a potential novel therapeutic approach. In this Perspective, we highlight the structures, the biological functions, regulatory mechanisms, relevant signaling pathways, and associations with cancer development of PRMT5, as well as the recent advances in drug discovery strategies targeting PRMT5. The challenges, opportunities, and future directions for developing PRMT5 inhibitors and degraders are also discussed.

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来源期刊

Bioorganic & Medicinal Chemistry 医学-生化与分子生物学

CiteScore

6.80

自引率

2.90%

发文量

413

审稿时长

17 days

期刊介绍： Bioorganic & Medicinal Chemistry provides an international forum for the publication of full original research papers and critical reviews on molecular interactions in key biological targets such as receptors, channels, enzymes, nucleotides, lipids and saccharides. The aim of the journal is to promote a better understanding at the molecular level of life processes, and living organisms, as well as the interaction of these with chemical agents. A special feature will be that colour illustrations will be reproduced at no charge to the author, provided that the Editor agrees that colour is essential to the information content of the illustration in question.