Drug discovery considerations in the development of covalent inhibitors

被引：161

作者：

Mah, Robert ^{[1
]}

Thomas, Jason R. ^{[2
]}

Shafer, Cynthia M. ^{[3
]}

机构：

[1] Novartis Inst Biomed Res, Global Discovery Chem Oncol & Exploratory Chem, CH-4057 Basel, Switzerland

[2] Novartis Inst Biomed Res, Dev & Mol Pathways, Cambridge, MA 02139 USA

[3] Novartis Inst Biomed Res, Global Discovery Chem Oncol & Exploratory Chem, Emeryville, CA 94608 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 01期

关键词：

Covalent inhibitor; Targeted covalent inhibitor (TCI); Mechanism-based inhibitor; k(inact)/K-i; Warhead reactivity; Activity-based protein profiling (ABPP); Click chemistry; IRREVERSIBLE INHIBITORS; KINASE; BINDING; REACTIVITY; DESIGN; MECHANISM; PROTEASE; TARGET; POTENT; ASSAY;

D O I：

10.1016/j.bmcl.2013.10.003

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In recent years, the number of drug candidates with a covalent mechanism of action progressing through clinical trials or being approved by the FDA has increased significantly. And as interest in covalent inhibitors has increased, the technical challenges for characterizing and optimizing these inhibitors have become evident. A number of new tools have been developed to aid this process, but these have not gained wide-spread use. This review will highlight a number of methods and tools useful for prosecuting covalent inhibitor drug discovery programs. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.

引用

页码：33 / 39

页数：7

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