论文标题：Discovery of small molecule degraders for modulating cell cycle

期刊： Frontiers of Medicine

作者：Liguo Wang, Zhouli Yang, Guangchen Li, Yongbo Liu, Chao Ai, Yu Rao

发表时间：15 Oct 2023

DOI：10.1007/s11684-023-1027-5

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导 读

清华大学艾超和饶燏等在Frontiers of Medicine发表综述论文《细胞周期调控小分子降解剂的发现》（Discovery of small molecule degraders for modulating cell cycle）。本文综述了利用PROTACs和分子胶技术开发靶向CDK/细胞周期蛋白的小分子降解剂的最新进展——突破了传统抑制剂的局限性，为肿瘤等细胞周期相关疾病提供了选择性降解治疗的新策略，并展望了计算机辅助设计和高通量筛选的未来发展方向。

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、蛋白质表达以及细胞分裂。细胞周期的失调与多种疾病相关。细胞周期蛋白依赖性激酶（CDKs）及其相应的细胞周期蛋白是调控细胞周期的主要蛋白质。相较于传统抑制策略，一种被称为蛋白水解靶向嵌合体（PROTACs）和分子胶的新方法能够消除CDKs和细胞周期蛋白的酶活性及支架功能，实现靶向降解。近年来，PROTACs和分子胶技术领域发展迅速。本文旨在系统综述CDKs和细胞周期蛋白降解剂的最新研究进展，重点解析各CDK降解剂的选择性、应用场景、验证方法及研究现状。此外，本文还探讨了针对目前尚未开发降解剂的CDK成员的潜在开发策略。综上所述，本文全面总结了CDK和细胞周期蛋白降解剂领域的最新研究进展，为该领域的科研人员提供了重要参考。

期刊介绍

Frontiers of Medicine专注于发表临床医学和基础医学领域的最新研究成果，旨在通过全球医疗专业人员之间的交流促进健康和医疗保健的发展。该刊采用严格的同行评审和编辑流程，确保发表的文章的科学准确性、新颖性和重要性。

原文信息

标题

Discovery of small molecule degraders for modulating cell cycle

作者

Liguo Wang¹, Zhouli Yang¹, Guangchen Li¹, Yongbo Liu1, Chao Ai², Yu Rao¹

机构

1. MOE Key Laboratory of Protein Sciences, School of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing 100084, China

2. Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China

通讯作者

Chao Ai, Yu Rao

引用这篇文章

Liguo Wang, Zhouli Yang, Guangchen Li, Yongbo Liu, Chao Ai, Yu Rao. Discovery of small molecule degraders for modulating cell cycle. Front. Med., 2023, 17(5): 823–854 https://doi.org/10.1007/s11684-023-1027-5

https://journal.hep.com.cn/fmd/EN/10.1007/s11684-023-1027-5

https://link.springer.com/article/10.1007/s11684-023-1027-5

感谢作者对Frontiers of Medicine的信任和支持。

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