title: Designed covalent allosteric modulators: an emerging paradigm in drug discovery.
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.
authors.affiliation: 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.
authors.forename: Shaoyong
authors.initials: S
authors.lastname: Lu
authors.affiliation: 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.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000494:Allosteric Regulation; D055808:Drug Discovery; D006801:Humans; D008024:Ligands; D011485:Protein Binding
chemical_list: D008024:Ligands