The use of virtual screening and differential scanning fluorimetry for the rapid identification of fragments active against MEK1.

Authors :: 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
Rak A
Source :: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2013 Jun 15; Vol. 23 (12), pp. 3620-6. Date of Electronic Publication: 2013 Apr 10.
Publication Year :: 2013
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.<br /> (Copyright © 2013 Elsevier Ltd. All rights reserved.)

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

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