Small-molecule degraders of cyclin-dependent kinase protein: a review

Proteolysis-targeting chimeras are a new modality of chemical tools and potential therapeutics involving the induction of protein degradation. Cyclin-dependent kinase (CDK) protein, which is involved in cycles and transcription cycles, participates in regulation of the cell cycle, transcription and splicing. Proteolysis-targeting chimeras targeting CDKs show several advantages over traditional CDK small-molecule inhibitors in potency, selectivity and drug resistance. In addition, the discovery of molecule glues promotes the development of CDK degraders. Herein, the authors describe the existing CDK degraders and focus on the discussion of the structural characteristics and design of these degraders.

Automated summary

Proteolysis-targeting chimeras are a new modality of chemical tools and potential therapeutics that induce protein degradation, with CDK-targeting degraders showing advantages in potency, selectivity, and drug resistance compared to traditional CDK inhibitors. The discovery of molecule glues has further promoted the development of CDK degraders, with a focus on discussing the structural characteristics and design of these degraders.