Screening and activity of PPARδ agonists based on pharmacophore model
Objective To screen the compounds with PPARδ agonizing activity.Methods PPARδpharmacophore model was established to screen 7.8 million small molecules in the Top Science database.Docking analysis was used to screen the binding mode and target selectivity between compounds and receptors.PPARδ agonists were obtained by in vitro activity experiment after identifying the hits with molecular dynamics simulation.Results Totally 24 potential PPARδ agonists were obtained by computer virtual screening.Molecular docking indicated that compounds 3,5,and 9 were potential PPARδ selective agonists and showed certain PPARδ activity in the in vitro activity tests.Conclusion Compound 9 can be used as a hit for structural iterative optimization,which lays a foundation for further development of PPARδ agonists with stronger in vitro activity(EC50=17.66 μmol·L-1).
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