1. The use of virtual screening and differential scanning fluorimetry for the rapid identification of fragments active against MEK1.
- Author
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Amaning K, Lowinski M, Vallee F, Steier V, Marcireau C, Ugolini A, Delorme C, Foucalt F, McCort G, Derimay N, Andouche C, Vougier S, Llopart S, Halland N, and Rak A
- Subjects
- Crystallography, X-Ray, Drug Evaluation, Preclinical methods, Enzyme Inhibitors chemistry, Humans, MAP Kinase Kinase 1 chemistry, MAP Kinase Kinase 1 metabolism, Models, Molecular, Phosphorylation, Structure-Activity Relationship, Enzyme Inhibitors pharmacology, Fluorometry methods, MAP Kinase Kinase 1 antagonists & inhibitors
- Abstract
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., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Published
- 2013
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