Applications of covalent chemistry in targeted protein degradation

Proteolysis-targeting chimeras (PROTACs) and targeted covalent inhibitors (TCIs) are currently two exciting strategies in the fields of chemical biology and drug discovery. Extensive research in these two fields has been conducted, and significant progress in these fields has resulted in many clinical candidates, some of which have been approved by FDA. Recently, a novel concept termed covalent PROTACs that combine these two strategies has emerged and gained an increasing interest in the past several years. Herein, we briefly review and highlight the mechanism and advantages of TCIs and PROTACs, respectively, and the recent development of covalent PROTACs using irreversible and reversible covalent chemistry.

Automated summary

Proteolysis-targeting chimeras (PROTACs) and targeted covalent inhibitors (TCIs) are two exciting strategies in the fields of chemical biology and drug discovery. The emergence of covalent PROTACs, which combine these two strategies, has gained increasing interest in recent years. This review highlights the mechanism and advantages of TCIs and PROTACs, and discusses the recent development of covalent PROTACs using irreversible and reversible covalent chemistry.