Targeting epigenetic reader domains by chemical biology.

Over the past years, growing interest toward post-translational modifications (PTMs) of histones and nonhistone proteins has prompted academia and industrial research groups to develop different approaches to better understand the link between PTMs and pathological states. Selective recognition of PTMs is carried out by reader modules, which mediate the biological readout of epigenetic mechanisms. Progress in medicinal chemistry and chemical biology has contributed to corroborate the role of reader domains in chromatin-binding proteins as potential therapeutic targets. Here, we review the state-of-the-art of the most important small molecules developed to date, with a particular attention on contemporary chemical biology approaches, including photoaffinity probes, cyclic peptides, bifunctional inhibitors, and PROTAC degraders.

Informations de copyright

Copyright © 2020 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest statement The Ciulli laboratory receives or has received sponsored research support from Amphista therapeutics, Boehringer Ingelheim, Eisai, Nurix, and Ono Pharmaceuticals. AC is a scientific founder, shareholder, nonexecutive director, and consultant of Amphista Therapeutics, a company that is developing targeted protein degradation therapeutic platforms. The remaining authors report no competing interests.