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Curr Opin Chem Biol. 2019 Jun;50:111-119. doi: 10.1016/j.cbpa.2019.02.022. Epub 2019 Apr 17.

Targeted protein degradation: elements of PROTAC design.

Author information

1
Molecular, Cellular, and Developmental Biology Department, Yale University, 219 Prospect Street, KBT 400, New Haven, CT, 06511, United States.
2
Molecular, Cellular, and Developmental Biology Department, Yale University, 219 Prospect Street, KBT 400, New Haven, CT, 06511, United States. Electronic address: craig.crews@yale.edu.

Abstract

Targeted protein degradation using Proteolysis Targeting Chimeras (PROTACs) has emerged as a novel therapeutic modality in drug discovery. PROTACs mediate the degradation of select proteins of interest (POIs) by hijacking the activity of E3 ubiquitin ligases for POI ubiquitination and subsequent degradation by the 26S proteasome. This hijacking mechanism has been used to degrade various types of disease-relevant POIs. In this review, we aim to highlight the recent advances in targeted protein degradation and describe the challenges that need to be addressed in order to efficiently develop potent PROTACs.

PMID:
31004963
DOI:
10.1016/j.cbpa.2019.02.022

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