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Current Topics in Medicinal Chemistry

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ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

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Current Frontiers

The Present and Future of Novel Protein Degradation Technology

Author(s): Liwen Xia, Wei Liu, Yinsen Song, Hailiang Zhu* and Yongtao Duan*

Volume 19, Issue 20, 2019

Page: [1784 - 1788] Pages: 5

DOI: 10.2174/1568026619666191011162955

Abstract

Proteolysis targeting chimeras (PROTACs), as a novel therapeutic modality, play a vital role in drug discovery. Each PROTAC contains three key parts; a protein-of-interest (POI) ligand, a E3 ligase ligand, and a linker. These bifunctional molecules could mediate the degradation of POIs by hijacking the activity of E3 ubiquitin ligases for POI ubiquitination and subsequent degradation via the ubiquitin proteasome system (UPS). With several advantages over other therapeutic strategies, PROTACs have set off a new upsurge of drug discovery in recent years. ENDTAC, as the development of PROTACs technology, is now receiving more attention. In this review, we aim to summarize the rapid progress from 2018 to 2019 in protein degradation and analyze the challenges and future direction that need to be addressed in order to efficiently develop potent protein degradation technology.

Keywords: PROTACs, ENDTAC, degradation, progress, challenges, UPS.

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