Selectivity On-target of Bromodomain Chemical Probes by Structure-guided Medicinal Chemistry and Chemical Biology

Overview

Journal Future Med Chem

Specialties Chemistry
Pharmacy

Date 2016 May 20

PMID 27193077

Citations 19

Authors

Carles Galdeano

Alessio Ciulli

Affiliations

Soon will be listed here.

Abstract

Targeting epigenetic proteins is a rapidly growing area for medicinal chemistry and drug discovery. Recent years have seen an explosion of interest in developing small molecules binding to bromodomains, the readers of acetyl-lysine modifications. A plethora of co-crystal structures has motivated focused fragment-based design and optimization programs within both industry and academia. These efforts have yielded several compounds entering the clinic, and many more are increasingly being used as chemical probes to interrogate bromodomain biology. High selectivity of chemical probes is necessary to ensure biological activity is due to an on-target effect. Here, we review the state-of-the-art of bromodomain-targeting compounds, focusing on the structural basis for their on-target selectivity or lack thereof. We also highlight chemical biology approaches to enhance on-target selectivity.

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