Designed covalent allosteric modulators: an emerging paradigm in drug discovery

Shaoyong Lu; Jian Zhang

doi:10.1016/j.drudis.2016.11.013

Designed covalent allosteric modulators: an emerging paradigm in drug discovery

Drug Discov Today. 2017 Feb;22(2):447-453. doi: 10.1016/j.drudis.2016.11.013. Epub 2016 Nov 22.

Authors

Shaoyong Lu¹, Jian Zhang²

Affiliations

¹ Department of Pathophysiology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, China.
² Department of Pathophysiology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, China; Medicinal Bioinformatics Center, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, China. Electronic address: jian.zhang@sjtu.edu.cn.

PMID: 27888140
DOI: 10.1016/j.drudis.2016.11.013

Abstract

Covalent allosteric modulators possess the pharmacological advantages (high potency, extended duration of action and low drug resistance) of covalent ligands and the additional benefit of the higher specificity and lower toxicity of allosteric modulators. This approach is gaining increasing recognition as a valuable tool in drug discovery. Here, we review the recent advances in the design of covalent allosteric modulators with an emphasis on successful examples. A broad spectrum of protein targets capable of being modulated by them reflects the prevalence of this strategy. We also discuss the challenges and future directions in the development of covalent allosteric modulators.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Allosteric Regulation
Drug Discovery*
Humans
Ligands
Protein Binding

Substances

Ligands