Covalent fragment libraries in drug discovery
| Autor: | Péter Ábrányi-Balogh, Aaron Keeley, László Petri, György M. Keserű |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Pharmacology Proteome Chemistry Drug discovery Proteins Computational biology 3. Good health Small Molecule Libraries 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Fragment (logic) Covalent bond 030220 oncology & carcinogenesis Proteins metabolism Drug Discovery Humans |
| Zdroj: | Drug Discovery Today |
| ISSN: | 1359-6446 |
| DOI: | 10.1016/j.drudis.2020.03.016 |
| Popis: | Targeted covalent inhibitors and chemical probes have become integral parts of drug discovery approaches. Given the advantages of fragment-based drug discovery, screening electrophilic fragments emerged as a promising alternative to discover and validate novel targets and to generate viable chemical starting points even for targets that are barely tractable. In this review, we present recent principles and considerations in the design of electrophilic fragment libraries from the selection of the appropriate covalent warhead through the design of the covalent fragment to the compilation of the library. We then summarize recent screening methodologies of covalent fragments against surrogate models, proteins, and the whole proteome, or living cells. Finally, we highlight recent drug discovery applications of covalent fragment libraries. |
| Databáze: | OpenAIRE |
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