College of Pharmaceutical Science, Institute of Drug Development & Chemical Biology, Zhejiang University of Technology, Hangzhou 310014, P.R. China.
Curr Med Chem. 2023;30(27):3060-3089. doi: 10.2174/0929867329666220829151257.
Protein lysine methylation is a significant protein post-translational modification (PTMs) and has a key function in epigenetic regulation. Protein lysine methyltransferase (PKMTs) mainly catalyzes the lysine methylation of various core histones and a few non-histone proteins. It has been observed that aberrant activity of PKMTs has been found in many cancers and other diseases, and some PKMT inhibitors have been discovered and progressed to clinical trials. This field developed rapidly and has aroused great interest. In this paper, we reviewed the biochemical and biological activities of PKMTs and their association with various cancers. Selective small-molecule inhibitors, including their chemical structure, structure-activity relationship, and in vitro/vivo studies, are also described to provide ideas for the discovery of highly potent, selective PKMT inhibitors.
蛋白质赖氨酸甲基化是一种重要的蛋白质翻译后修饰（PTMs），在表观遗传调控中具有关键作用。蛋白质赖氨酸甲基转移酶（PKMTs）主要催化各种核心组蛋白和一些非组蛋白蛋白质的赖氨酸甲基化。已经观察到，PKMTs 的异常活性已在许多癌症和其他疾病中发现，并且已经发现并推进了一些 PKMT 抑制剂进入临床试验。该领域发展迅速，引起了极大的兴趣。本文综述了 PKMTs 的生化和生物学活性及其与各种癌症的关系。还描述了选择性小分子抑制剂，包括它们的化学结构、构效关系和体外/体内研究，为发现高效、选择性的 PKMT 抑制剂提供了思路。
