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