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Selection, Application, and Validation of a Set of Molecular Descriptors for Nuclear Receptor Ligands

[ Vol. 7 , Issue. 5 ]

Author(s):

Eugene L. Stewart, Peter J. Brown, James A. Bentley and Timothy M. Willson   Pages 407 - 412 ( 6 )

Abstract:


A methodology for the selection and validation of nuclear receptor ligand chemical descriptors is described. After descriptors for a targeted chemical space were selected, a virtual screening methodology utilizing this space was formulated for the identification of potential NR ligands from our corporate collection. Using simple descriptors and our virtual screening method, we are able to quickly identify potential NR ligands from a large collection of compounds. As validation of the virtual screening procedure, an 8, 000- membered NR targeted set and a 24, 000-membered diverse control set of compounds were selected from our inhouse general screening collection and screened in parallel across a number of orphan NR FRET assays. For the two assays that provided at least one hit per set by the established minimum pEC50 for activity, the results showed a 2-fold increase in the hit-rate of the targeted compound set over the diverse set.

Keywords:

targeted selection, orphan nuclear receptors, bcuts, diversesolutions

Affiliation:

Discovery Research,GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709,USA.



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