Current Computer-Aided Drug Design

Subhash C. Basak
Departments of Chemistry, Biochemistry & Molecular Biology University of Minnesota Duluth
Duluth, MN 55811


3D-QSAR Based Pharmacophore Modeling and Virtual Screening for Identification of Novel G Protein-Coupled Receptor40 Agonists

Author(s): Peng Lu, Yubin Wang, Ping Kai Ouyang, Jinxiong She, Mingfang He.


Pharmacophore models of G protein-coupled receptor40 (GPR40) agonists were developed using Discovery Studio V2.1. One hydrogen bond acceptor and three hydrophobic features, Hypo 1 which was the best hypothesis, had a correlation co-efficient of 0.971, cost difference of 73.041, and RMSD 0.680. This model was validated by test set, Fischer randomization test and decoy set. Subsequently, Hypo 1 was employed as a 3D query to identify potent molecules from chembridge database. 21 compounds were identified with estimated EC50 less than 500 nM. Seven top-scored hit compounds were chosen for further evaluation in FLIPR assay and two compounds were discovered as potent GPR40 agonists.

Keywords: 3D-QSAR-pharmacophore, discovery studio, GPR40 agonists, HypoGen, virtual screening.

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Article Details

Year: 2015
Page: [51 - 56]
Pages: 6
DOI: 10.2174/1573409911666150529125814
Price: $58