Tong Chao, Chang Xiujin, Qu Fangui, Bian Jinlei, Wang Jubo, Li Zhiyu, Xu Xi
Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjin, 211198, China.
Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjin, 211198, China.
Eur J Med Chem. 2024 Mar 5;267:116212. doi: 10.1016/j.ejmech.2024.116212. Epub 2024 Feb 10.
Protein methylation is a post-translational modification (PTM) that organisms undergo. This process is considered a part of epigenetics research. In recent years, there has been an increasing interest in protein methylation, particularly histone methylation, as research has advanced. Methylation of histones is a dynamic process that is subject to fine control by histone methyltransferases and demethylases. In addition, many non-histone proteins also undergo methylation, and these modifications collectively regulate physiological phenomena, including RNA transcription, translation, signal transduction, DNA damage response, and cell cycle. Protein arginine methylation is a crucial aspect of protein methylation, which plays a significant role in regulating the cell cycle and repairing DNA. It is also linked to various diseases. Therefore, protein arginine methyltransferases (PRMTs) that are involved in this process have gained considerable attention as a potential therapeutic target for treating diseases. Several PRMT inhibitors are in phase I/II clinical trials. This paper aims to introduce the structure, biochemical functions, and bioactivity assays of PRMTs. Additionally, we will review the structure-function of currently popular PRMT inhibitors. Through the analysis of various data on known PRMT inhibitors, we hope to provide valuable assistance for future drug design and development.
蛋白质甲基化是生物体所经历的一种翻译后修饰（PTM）。这一过程被认为是表观遗传学研究的一部分。近年来，随着研究的进展，人们对蛋白质甲基化，尤其是组蛋白甲基化的兴趣日益浓厚。组蛋白甲基化是一个动态过程，受到组蛋白甲基转移酶和去甲基化酶的精细调控。此外，许多非组蛋白也会发生甲基化，这些修饰共同调节生理现象，包括RNA转录、翻译、信号转导、DNA损伤反应和细胞周期。蛋白质精氨酸甲基化是蛋白质甲基化的一个关键方面，在调节细胞周期和修复DNA中起重要作用。它还与多种疾病有关。因此，参与这一过程的蛋白质精氨酸甲基转移酶（PRMTs）作为治疗疾病的潜在治疗靶点受到了相当大的关注。几种PRMT抑制剂正处于I/II期临床试验中。本文旨在介绍PRMTs的结构、生化功能和生物活性测定。此外，我们将综述目前流行的PRMT抑制剂的结构功能。通过对已知PRMT抑制剂的各种数据进行分析，我们希望为未来的药物设计和开发提供有价值的帮助。
