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Parallel Interrogation of β-Arrestin2 Recruitment for Ligand Screening on a GPCR-Wide Scale using PRESTO-Tango Assay
Published on: March 10, 2020
A comparison of ligand based virtual screening methods and application to corticotropin releasing factor 1 receptor
Gary Tresadern1, Daniele Bemporad, Trevor Howe
1Johnson & Johnson, Pharmaceutical Research & Development, Janssen-Cilag S.A., Calle Jarama, 75, Poligono Industrial, 45007 Toledo, Spain. gtresade@its.jnj.com
Abstract:
Ligand based virtual screening approaches were applied to the CRF1 receptor. We compared ECFP6 fingerprints, FTrees, Topomers, Cresset FieldScreen, ROCS OpenEye shape Tanimoto, OpenEye combo-score and OpenEye electrostatics. The 3D methods OpenEye Shape Tanimoto, combo-score and Topomers performed the best at separating actives from inactives in retrospective experiments. By virtue of their higher enrichment the same methods identified more active scaffolds. However, amongst a given number of active compounds the Cresset and OpenEye electrostatic methods contained more scaffolds and returned ranked compounds with greater diversity. A selection of the methods were employed to recommend compounds for screening in a prospective experiment. New CRF1 actives antagonists were found. The new actives contained different underlying chemical architecture to the query molecules, results indicative of successful scaffold-hopping.
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