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The use of virtual screening and differential scanning fluorimetry for the rapid identification of fragments active against MEK1 |
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| Authors: | Kwame Amaning Maryse Lowinski Francois Vallee Valerie Steier Christophe Marcireau Antonio Ugolini Cecile Delorme Frédéric Foucalt Gary McCort Nathalie Derimay Cyrielle Andouche Stephanie Vougier Sylvie Llopart Nis Halland Alexey Rak |
| Affiliation: | 1. Sanofi, Structure Design and Informatics,13 Quai Guesde, B.P.14, F-94408 Vitry-Sur-Seine, France;2. Oncology Group, Vitry-Sur-Seine, France;3. Lead Identification Technologies, Strasbourg, France;4. Lead Identification Technologies, Vitry-Sur-Seine, France;5. Protein Production and Characterisation, Toulouse, France;6. Parallel Synthesis and Natural Product Chemistry, Frankfurt, Germany |
| 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. |
| Keywords: | Fragment screening Virtual screening Differential scanning fluorimetry MEK1 |
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