Mount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences, Oncological Sciences and Neuroscience, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
Mount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences, Oncological Sciences and Neuroscience, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
Curr Opin Chem Biol. 2023 Oct;76:102356. doi: 10.1016/j.cbpa.2023.102356. Epub 2023 Jun 26.
Over the last several decades, there has been continued interest in developing novel therapeutic approaches targeting protein lysine methyltransferases (PKMTs). Along with PKMT inhibitors, targeted protein degradation (TPD) has emerged as a promising strategy to attenuate aberrant PKMT activity. Particularly, proteolysis targeting chimeras (PROTACs) effectively eliminate PKMTs of interest, suppressing all enzymatic and non-enzymatic functions. PROTACs and other TPD approaches add new depth to PKMT research and novel therapeutics discovery. This review focuses on recent advances in PKMT degrader and inhibitor development over the last several years.
在过去的几十年中，人们一直致力于开发针对蛋白赖氨酸甲基转移酶（PKMTs）的新型治疗方法。除了 PKMT 抑制剂外，靶向蛋白降解（TPD）已成为一种有前途的策略，可以减弱异常 PKMT 活性。特别是，蛋白水解靶向嵌合体（PROTACs）可以有效地消除目标 PKMT，抑制所有酶和非酶功能。PROTACs 和其他 TPD 方法为 PKMT 研究和新型治疗药物的发现增添了新的深度。本综述重点介绍了过去几年中 PKMT 降解剂和抑制剂开发的最新进展。
