Covalent inhibitors design and discovery

被引：234

作者：

De Cesco, Stephane ^{[1
]}

Kurian, Jerry ^{[1
]}

Dufresne, Caroline ^{[1
]}

Mittermaier, Anthony K. ^{[1
]}

Moitessier, Nicolas ^{[1
]}

机构：

[1] McGill Univ, Dept Chem, 801 Sherbrooke St W, Montreal, PQ H3A 0B8, Canada

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2017年 / 138卷

关键词：

Covalent drugs; Drug design; Binding kinetics; Docking; TARGET RESIDENCE TIME; ACETYLGLUCOSAMINE ENOLPYRUVYL TRANSFERASE; UDP-N-ACETYLGLUCOSAMINE; DIPEPTIDYL PEPTIDASE-IV; ERBB FAMILY BLOCKER; DRUG DISCOVERY; KINASE INHIBITORS; NATURAL-PRODUCTS; IRREVERSIBLE INHIBITORS; ALKYLATING-AGENTS;

D O I：

10.1016/j.ejmech.2017.06.019

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In the history of therapeutics, covalent drugs occupy a very distinct category. While representing a significant fraction of the drugs on the. market, very few have been deliberately designed to interact covalently with their biological target. In this review, the prevalence of covalent drugs will first be briefly covered, followed by an introduction to their mechanisms of action and more detailed discussions of their discovery and the development of safe and efficient covalent enzyme inhibitors. All stages of a drug discovery program will be covered, from target considerations to lead optimization, strategies to tune reactivity and computational methods. The goal of this article is to provide an overview of the field and to outline good practices that are needed for the proper assessment and development of covalent inhibitors as well as a good understanding of the potential and limitations of current computational methods for the design of covalent drugs. (C) 2017 Elsevier Masson SAS. All rights reserved.

引用

页码：96 / 114

页数：19

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