Discovery and Development of the Quininib Series of Ocular Drugs

DC FieldValueLanguage
dc.contributor.authorMahon, Niamh-
dc.contributor.authorSlater, Kayleigh-
dc.contributor.authorO'Brien, Justine-
dc.contributor.authorAlvarez, Yolanda-
dc.contributor.authorReynolds, Alison-
dc.contributor.authorKennedy, Breandán-
dc.date.accessioned2022-08-09T07:57:46Z-
dc.date.available2022-08-09T07:57:46Z-
dc.date.copyright2022 Mary Ann Lieberten_US
dc.date.issued2022-01-28-
dc.identifier.citationJournal of Ocular Pharmacology and Therapeuticsen_US
dc.identifier.issn1557-7732-
dc.identifier.urihttp://hdl.handle.net/10197/13046-
dc.description.abstractThe quininib series is a novel collection of small-molecule drugs with antiangiogenic, antivascular permeability, anti-inflammatory, and antiproliferative activity. Quininib was initially identified as a drug hit during a random chemical library screen for determinants of developmental ocular angiogenesis in zebrafish. To enhance drug efficacy, novel quininib analogs were designed by applying medicinal chemistry approaches. The resulting quininib drug series has efficacy in in vitro and ex vivo models of angiogenesis utilizing human cell lines and tissues. In vivo, quininib drugs reduce pathological angiogenesis and retinal vascular permeability in rodent models. Quininib acts as a cysteinyl leukotriene (CysLT) receptor antagonist, revealing new roles of these G-protein-coupled receptors in developmental angiogenesis of the eye and unexpectedly in uveal melanoma (UM). The quininib series highlighted the potential of CysLT receptors as therapeutic targets for retinal vasculopathies (e.g., neovascular age-related macular degeneration, diabetic retinopathy, and diabetic macular edema) and ocular cancers (e.g., UM).en_US
dc.description.sponsorshipEnterprise Irelanden_US
dc.description.sponsorshipEuropean Commission Horizon 2020en_US
dc.description.sponsorshipHealth Research Boarden_US
dc.description.sponsorshipIrish Research Councilen_US
dc.description.sponsorshipScience Foundation Irelanden_US
dc.language.isoenen_US
dc.publisherMary Ann Lieberten_US
dc.rightsFinal publication is available from Mary Ann Liebert, Inc., publishers http://dx.doi.org/10.1089/jop.2021.0074en_US
dc.subjectQuininib drug seriesen_US
dc.subjectOcular angiogenesisen_US
dc.subjectCysteinyl leukotriene receptorsen_US
dc.subjectZebrafishen_US
dc.subjectPhenotype-based drug discoveryen_US
dc.titleDiscovery and Development of the Quininib Series of Ocular Drugsen_US
dc.typeJournal Articleen_US
dc.statusPeer revieweden_US
dc.identifier.volume38en_US
dc.identifier.issue1en_US
dc.identifier.startpage33en_US
dc.identifier.endpage42en_US
dc.identifier.doi10.1089/jop.2021.0074-
dc.neeo.contributorMahon|Niamh|aut|-
dc.neeo.contributorSlater|Kayleigh|aut|-
dc.neeo.contributorO'Brien|Justine|aut|-
dc.neeo.contributorAlvarez|Yolanda|aut|-
dc.neeo.contributorReynolds|Alison|aut|-
dc.neeo.contributorKennedy|Breandán|aut|-
dc.identifier.grantid11/TIDA/B1966-
dc.identifier.grantidCF/20111319-
dc.identifier.grantid101007931-
dc.rights.licensehttps://creativecommons.org/licenses/by/3.0/ie/en_US
dc.identifier.pmid35089801-
item.grantfulltextopen-
item.fulltextWith Fulltext-
Appears in Collections:Conway Institute Research Collection
Biomolecular and Biomedical Science Research Collection
Veterinary Medicine Research Collection
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