title: Potent Small Agonists of Protease Activated Receptor 2.
abstract: Many proteases cut the PAR2 N-terminus resulting in conformational changes that activate cells. Synthetic peptides corresponding to newly exposed N-terminal sequences of PAR2 also activate the receptor at micromolar concentrations. PAR2-selective small molecules reported here induce PAR2-mediated intracellular calcium signaling at nanomolar concentrations (EC50 = 15-100 nM, iCa(2+), CHO-hPAR2 cells). These are the most potent and efficient small molecule ligands to activate PAR2-mediated calcium release and chemotaxis, including for human breast and prostate cancer cells.
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland , Brisbane, Qld 4072, Australia.
authors.forename: Mei-Kwan
authors.initials: MK
authors.lastname: Yau
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland , Brisbane, Qld 4072, Australia.
authors.forename: Jacky Y
authors.initials: JY
authors.lastname: Suen
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland , Brisbane, Qld 4072, Australia.
authors.forename: Weijun
authors.initials: W
authors.lastname: Xu
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland , Brisbane, Qld 4072, Australia.
authors.forename: Junxian
authors.initials: J
authors.lastname: Lim
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland , Brisbane, Qld 4072, Australia.
authors.forename: Ligong
authors.initials: L
authors.lastname: Liu
authors.affiliation: Translational Research Institute, Mater Research Institute, The University of Queensland , Woolloongabba, Qld 4102, Australia.
authors.forename: Mark N
authors.initials: MN
authors.lastname: Adams
authors.affiliation: Translational Research Institute, Mater Research Institute, The University of Queensland , Woolloongabba, Qld 4102, Australia.
authors.forename: Yaowu
authors.initials: Y
authors.lastname: He
authors.affiliation: Translational Research Institute, Mater Research Institute, The University of Queensland , Woolloongabba, Qld 4102, Australia.
authors.forename: John D
authors.initials: JD
authors.lastname: Hooper
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland , Brisbane, Qld 4072, Australia.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Reid
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland , Brisbane, Qld 4072, Australia.
authors.forename: David P
authors.initials: DP
authors.lastname: Fairlie
keywords: Protease activated receptor 2; agonist; cyclohexylglycine; structure−activity relationships
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