The resurgence of covalent drugs

被引：1345
作者：
Singh, Juswinder [1 ]
Petter, Russell C. [1 ]
Baillie, Thomas A. [2 ]
Whitty, Adrian [3 ]
机构：
[1] Avila Therapeut, Waltham, MA 02453 USA
[2] Univ Washington, Sch Pharm, Seattle, WA 98195 USA
[3] Boston Univ, Metcalf Sci Ctr, Dept Chem, Boston, MA 02215 USA
来源：
NATURE REVIEWS DRUG DISCOVERY | 2011年 / 10卷 / 04期
关键词：
GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; IRREVERSIBLE INHIBITORS; METABOLIC-ACTIVATION; ABIRATERONE ACETATE; RESIDENCE TIME; EGF RECEPTOR; BINDING; DESIGN; FUTURE;
D O I：
10.1038/nrd3410
中图分类号：
Q81 [生物工程学（生物技术）]; Q93 [微生物学];
学科分类号：
071005 ; 0836 ; 090102 ; 100705 ;
摘要：
Covalent drugs have proved to be successful therapies for various indications, but largely owing to safety concerns, they are rarely considered when initiating a target-directed drug discovery project. There is a need to reassess this important class of drugs, and to reconcile the discordance between the historic success of covalent drugs and the reluctance of most drug discovery teams to include them in their armamentarium. This Review surveys the prevalence and pharmacological advantages of covalent drugs, discusses how potential risks and challenges may be addressed through innovative design, and presents the broad opportunities provided by targeted covalent inhibitors.
引用
收藏
页码：307 / 317
页数：11
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