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

作者：Amaning Kwame^*; Lowinski Maryse; Vallee Francois; Steier Valerie; Marcireau Christophe; Ugolini Antonio; Delorme Cecile; Foucalt Frederic; McCort Gary; Derimay Nathalie; Andouche Cyrielle; Vougier Stephanie; Llopart Sylvie; Halland Nis; Rak Alexey

来源：Bioorganic & Medicinal Chemistry Letters, 2013, 23(12): 3620-3626.

DOI：10.1016/j.bmcl.2013.04.003

• Fragment screening
• Virtual screening
• Differential scanning fluorimetry
• MEK1

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.

• 出版日期2013-6-15