Title:The Present and Future of Novel Protein Degradation Technology
Volume: 19
Issue: 20
Author(s): Liwen Xia, Wei Liu, Yinsen Song, Hailiang Zhu*Yongtao Duan*
Affiliation:
- Henan Provincial Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou University, Zhengzhou, 450018,China
- Henan Provincial Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou University, Zhengzhou, 450018,China
Keywords:
PROTACs, ENDTAC, degradation, progress, challenges, UPS.
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.
