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dc.contributor.authorQin, CX
dc.contributor.authorMay, LT
dc.contributor.authorLi, R
dc.contributor.authorCao, N
dc.contributor.authorRosli, S
dc.contributor.authorMinh, D
dc.contributor.authorAlexander, AE
dc.contributor.authorHorlock, D
dc.contributor.authorBourke, JE
dc.contributor.authorYang, YH
dc.contributor.authorStewart, AG
dc.contributor.authorKaye, DM
dc.contributor.authorDu, X-J
dc.contributor.authorSexton, PM
dc.contributor.authorChristopoulos, A
dc.contributor.authorGao, X-M
dc.contributor.authorRitchie, RH
dc.date.accessioned2020-12-22T03:51:52Z
dc.date.available2020-12-22T03:51:52Z
dc.date.issued2017-02-07
dc.identifierpii: ncomms14232
dc.identifier.citationQin, C. X., May, L. T., Li, R., Cao, N., Rosli, S., Minh, D., Alexander, A. E., Horlock, D., Bourke, J. E., Yang, Y. H., Stewart, A. G., Kaye, D. M., Du, X. -J., Sexton, P. M., Christopoulos, A., Gao, X. -M. & Ritchie, R. H. (2017). Small-molecule-biased formyl peptide receptor agonist compound 17b protects against myocardial ischaemia-reperfusion injury in mice. NATURE COMMUNICATIONS, 8 (1), https://doi.org/10.1038/ncomms14232.
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/11343/257945
dc.description.abstractEffective treatment for managing myocardial infarction (MI) remains an urgent, unmet clinical need. Formyl peptide receptors (FPR) regulate inflammation, a major contributing mechanism to cardiac injury following MI. Here we demonstrate that FPR1/FPR2-biased agonism may represent a novel therapeutic strategy for the treatment of MI. The small-molecule FPR1/FPR2 agonist, Compound 17b (Cmpd17b), exhibits a distinct signalling fingerprint to the conventional FPR1/FPR2 agonist, Compound-43 (Cmpd43). In Chinese hamster ovary (CHO) cells stably transfected with human FPR1 or FPR2, Compd17b is biased away from potentially detrimental FPR1/2-mediated calcium mobilization, but retains the pro-survival signalling, ERK1/2 and Akt phosphorylation, relative to Compd43. The pathological importance of the biased agonism of Cmpd17b is demonstrable as superior cardioprotection in both in vitro (cardiomyocytes and cardiofibroblasts) and MI injury in mice in vivo. These findings reveal new insights for development of small molecule FPR agonists with an improved cardioprotective profile for treating MI.
dc.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleSmall-molecule-biased formyl peptide receptor agonist compound 17b protects against myocardial ischaemia-reperfusion injury in mice
dc.typeJournal Article
dc.identifier.doi10.1038/ncomms14232
melbourne.affiliation.departmentPharmacology and Therapeutics
melbourne.source.titleNature Communications
melbourne.source.volume8
melbourne.source.issue1
dc.rights.licenseCC BY
melbourne.elementsid1183283
melbourne.contributor.authorStewart, Alastair
melbourne.contributor.authorQin, Chengxue
melbourne.contributor.authorRitchie, Rebecca
dc.identifier.eissn2041-1723
melbourne.accessrightsOpen Access


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