Wang Liguo, Yang Zhouli, Li Guangchen, Liu Yongbo, Ai Chao, Rao Yu
MOE Key Laboratory of Protein Sciences, School of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing, 100084, China.
Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, 102218, China.
Front Med. 2023 Oct;17(5):823-854. doi: 10.1007/s11684-023-1027-5. Epub 2023 Nov 8.
The cell cycle is a complex process that involves DNA replication, protein expression, and cell division. Dysregulation of the cell cycle is associated with various diseases. Cyclin-dependent kinases (CDKs) and their corresponding cyclins are major proteins that regulate the cell cycle. In contrast to inhibition, a new approach called proteolysis-targeting chimeras (PROTACs) and molecular glues can eliminate both enzymatic and scaffold functions of CDKs and cyclins, achieving targeted degradation. The field of PROTACs and molecular glues has developed rapidly in recent years. In this article, we aim to summarize the latest developments of CDKs and cyclin protein degraders. The selectivity, application, validation and the current state of each CDK degrader will be overviewed. Additionally, possible methods are discussed for the development of degraders for CDK members that still lack them. Overall, this article provides a comprehensive summary of the latest advancements in CDK and cyclin protein degraders, which will be helpful for researchers working on this topic.
细胞周期是一个复杂的过程，涉及DNA复制、蛋白质表达和细胞分裂。细胞周期失调与多种疾病相关。细胞周期蛋白依赖性激酶（CDK）及其相应的细胞周期蛋白是调节细胞周期的主要蛋白质。与抑制作用不同，一种名为蛋白酶靶向嵌合体（PROTAC）和分子胶的新方法可以消除CDK和细胞周期蛋白的酶促功能和支架功能，实现靶向降解。近年来，PROTAC和分子胶领域发展迅速。在本文中，我们旨在总结CDK和细胞周期蛋白降解剂的最新进展。将概述每种CDK降解剂的选择性、应用、验证情况及当前状态。此外，还讨论了为仍缺乏降解剂的CDK成员开发降解剂的可能方法。总体而言，本文全面总结了CDK和细胞周期蛋白降解剂的最新进展，这将有助于从事该主题研究的人员。
