Discovery of small molecule degraders for modulating cell cycle  

作　　者：Liguo Wang Zhouli Yang Guangchen Li Yongbo Liu Chao Ai Yu Rao 

机构地区：[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

出　　处：《Frontiers of Medicine》2023年第5期823-854,共32页医学前沿（英文版）

基　　金：supported by National Key R&D Program of China (Nos.2021YFA1302100,2020YFE0202200,and 2021YFA1300200);National Natural Science Foundation of China (No.82125034);Fellowship of China Postdoctoral Science Foundation (No.2021M701953);the Foundation of Shuimu Tsinghua Scholar Program (No.2021SM110).

摘　　要：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.

关 键 词：PROTAC molecular glue degrader cell cycle CDK CYCLIN 

分 类 号：R73[医药卫生—肿瘤]