The use of virtual screening and differential scanning fluorimetry for the rapid identification of fragments active against MEK1
| Autor: | Gary Mccort, Sylvie Llopart, Cyrielle Andouche, François Vallée, Cécile Delorme, Frédéric Foucalt, Maryse Lowinski, Nathalie Derimay, Kwame Amaning, Nis Halland, Antonio Ugolini, Valerie Steier, Alexey Rak, Christophe Marcireau, Stephanie Vougier |
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| Rok vydání: | 2013 |
| Předmět: |
Models
Molecular Virtual screening Chemistry Drug discovery In silico Organic Chemistry Clinical Biochemistry Drug Evaluation Preclinical MAP Kinase Kinase 1 Pharmaceutical Science Computational biology Crystallography X-Ray Biochemistry Molecular biology Rapid identification Structure-Activity Relationship Drug Discovery Molecular Medicine Humans Fluorometry Enzyme Inhibitors Phosphorylation Molecular Biology |
| Zdroj: | Bioorganicmedicinal chemistry letters. 23(12) |
| ISSN: | 1464-3405 |
| Popis: | We report the analysis of an in-house fragment screening campaign for the oncology target MEK1. The application of virtual screening (VS) as a primary fragment screening approach, followed by biophysical validation using differential screening fluorimetry (DSF), with resultant binding mode determination by X-ray crystallography (X-ray), is presented as the most time and cost-effective combination of in silico and in vitro methods to identify fragments. We demonstrate the effectiveness of the VS–DSF workflow for the early identification of fragments to both ‘jump-start’ the drug discovery project and to complement biochemical screening data. |
| Databáze: | OpenAIRE |
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