Issue 13, 2023

Chemically induced degradation of epigenetic targets

Abstract

Proteolysis-targeting chimeras (PROTACs) are heterobifunctional small molecules that induce the ternary complex formation between a protein-of-interest (POI) and an E3 ligase, leading to targeted polyubiquitination and degradation of the POI. Particularly, PROTACs have the distinct advantage of targeting both canonical and noncanonical functions of epigenetic targets over traditional inhibitors, which typically target canonical functions only, resulting in greater therapeutic efficacy. In this review, we methodically analyze published PROTAC degraders of epigenetic writer, reader, and eraser proteins and their in vitro and in vivo effects. We highlight the mechanism of action of these degraders and their advantages in targeting both canonical and noncanonical functions of epigenetic targets in the context of cancer treatment. Furthermore, we present a future outlook for this exciting field. Overall, pharmacological degradation of epigenetic targets has emerged as an effective and attractive strategy to thwart cancer progression and growth.

Graphical abstract: Chemically induced degradation of epigenetic targets

Supplementary files

Article information

Article type
Review Article
Submitted
09 feb. 2023
First published
14 jun. 2023

Chem. Soc. Rev., 2023,52, 4313-4342

Chemically induced degradation of epigenetic targets

M. Kabir, X. Yu, H. Ü. Kaniskan and J. Jin, Chem. Soc. Rev., 2023, 52, 4313 DOI: 10.1039/D3CS00100H

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