title: Repurposing Registered Drugs as Antagonists for Protease-Activated Receptor 2.
abstract: Virtual screening of a drug database identified Carvedilol, Loratadine, Nefazodone and Astemizole as PAR2 antagonists, after ligand docking and molecular dynamics simulations using a PAR2 homology model and a putative binding mode of a known PAR2 ligand. The drugs demonstrated competitive binding and antagonism of calcium mobilization and ERK1/2 phosphorylation in CHO-hPAR2 transfected cells, while inhibiting IL-6 secretion in PAR2 expressing MDA-MB-231 breast cancer cells. This research highlights opportunities for GPCR hit-finding from FDA-approved drugs.
authors.affiliation: Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland , Brisbane, Queensland 4072, Australia.
authors.forename: Weijun
authors.initials: W
authors.lastname: Xu
authors.affiliation: Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland , Brisbane, Queensland 4072, Australia.
authors.forename: Junxian
authors.initials: J
authors.lastname: Lim
authors.affiliation: Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland , Brisbane, Queensland 4072, Australia.
authors.forename: Chai-Yeen
authors.initials: CY
authors.lastname: Goh
authors.affiliation: Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland , Brisbane, Queensland 4072, Australia.
authors.forename: Jacky Y
authors.initials: JY
authors.lastname: Suen
authors.affiliation: Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland , Brisbane, Queensland 4072, Australia.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland , Brisbane, Queensland 4072, Australia.
authors.forename: Mei-Kwan
authors.initials: MK
authors.lastname: Yau
authors.affiliation: Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland , Brisbane, Queensland 4072, Australia.
authors.forename: Kai-Chen
authors.initials: KC
authors.lastname: Wu
authors.affiliation: Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland , Brisbane, Queensland 4072, Australia.
authors.forename: Ligong
authors.initials: L
authors.lastname: Liu
authors.affiliation: Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland , Brisbane, Queensland 4072, Australia.
authors.forename: David P
authors.initials: DP
authors.lastname: Fairlie
mesh_terms: D001667:Binding, Competitive; D055808:Drug Discovery; D058492:Drug Repositioning; D006801:Humans; D008954:Models, Biological; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D044464:Receptor, PAR-2 / Q000037:antagonists & inhibitors*
chemical_list: D044464:Receptor, PAR-2