title: The use of virtual screening and differential scanning fluorimetry for the rapid identification of fragments active against MEK1.
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.
authors: Sanofi, Structure Design and Informatics,13 Quai Guesde, B.P.14, F-94408 Vitry-Sur-Seine, France. kwame.amaning@sanofi.com
authors: Kwame
authors: K
authors: Amaning
authors: Maryse
authors: M
authors: Lowinski
authors: Francois
authors: F
authors: Vallee
authors: Valerie
authors: V
authors: Steier
authors: Christophe
authors: C
authors: Marcireau
authors: Antonio
authors: A
authors: Ugolini
authors: Cecile
authors: C
authors: Delorme
authors: Frédéric
authors: F
authors: Foucalt
authors: Gary
authors: G
authors: McCort
authors: Nathalie
authors: N
authors: Derimay
authors: Cyrielle
authors: C
authors: Andouche
authors: Stephanie
authors: S
authors: Vougier
authors: Sylvie
authors: S
authors: Llopart
authors: Nis
authors: N
authors: Halland
authors: Alexey
authors: A
authors: Rak
mesh_terms: D018360:Crystallography, X-Ray; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005470:Fluorometry / Q000379:methods*; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D010766:Phosphorylation; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D048369:MAP Kinase Kinase 1