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ID: ALA5244258

Journal: Eur J Med Chem

Title: PROTACs: New method to degrade transcription regulating proteins.

Authors: Hu B, Zhou Y, Sun D, Yang Y, Liu Y, Li X, Li H, Chen L.

Abstract: Transcription is the fundamental process in all living organisms. A variety of important proteins, such as NRs, BETs, HDACs and many others are involved in transcription process. In general, overexpression of these proteins would cause many diseases. Some approved therapeutics employed inhibitors to regulate the transcription process, however, the results are far from satisfying. Therefore, it is in high demand to develop new technology to improve the therapeutic effects. In recent years, proteolysis-targeting chimaera (PROTAC) turned out to be a novel efficient therapeutic method to treat various diseases which were caused by proteins overexpression. PROTAC molecules are bifunctional small molecules that simultaneously bind a target protein and an E3-ubiquitin ligase, thus causing ubiquitination and subsequent degradation of the target protein by the proteasome. In contrast to traditional inhibitors, PROTACs showed higher efficiency to tackle the diseases which were caused by protein overexpression due to their excellent performance for degrading target proteins in transcription regulation. In this review, 29 kinds of PROTACs targeting transcription regulator proteins are summarized, and meanwhile the advantages of PROTACs are highlighted. Furthermore, several examples of PROTACs regulating the transcription for the treatment of diseases and functioning as tools for biological research are also disscussed.

CiteXplore: 32858471

DOI: 10.1016/j.ejmech.2020.112698