Health & Environmental Research Online (HERO)


Print Feedback Export to File
7223295 
Journal Article 
Review 
Covalent inhibitors design and discovery 
De Cesco, S; Kurian, J; Dufresne, C; Mittermaier, AK; Moitessier, N; , 
2017 
Yes 
European Journal of Medicinal Chemistry
ISSN: 0223-5234
EISSN: 1768-3254 
Elsevier Masson s.r.l. 
138 
96-114 
English 
28651155 
WOS:000411297000009 
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. 
Binding kinetics; Covalent drugs; Docking; Drug design; acetylsalicylic acid; afatinib; azinomycin a; boceprevir; bortezomib; carfilzomib; chlormethine; clopidogrel; covalent inhibitor; enzyme inhibitor; esomeprazole; etacrynic acid; fosfomycin; functional group; lansoprazole; microcystin LR; natural product; odanacatib; penicillin G; rivastigmine; salinosporamide A; saxagliptin; showdomycin; telaprevir; tetrahydrolipstatin; unclassified drug; biological product; covalent bond; drug binding; drug design; drug mechanism; drug structure; kinetic parameters; protein analysis; quantum mechanics; Review; chemistry; drug development; human; kinetics; quantum theory; synthesis; Biological Products; Drug Discovery; Humans; Kinetics; Quantum Theory 
Other
• Harmful Algal Blooms- Health Effects
     April 2021 Literature Search
          Scopus