Discovery and Development of the Quininib Series of Ocular Drugs

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Title: Discovery and Development of the Quininib Series of Ocular Drugs
Authors: Mahon, NiamhSlater, KayleighO'Brien, JustineAlvarez, YolandaReynolds, AlisonKennedy, Breandán
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Date: 28-Jan-2022
Online since: 2022-08-09T07:57:46Z
Abstract: The 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).
Funding Details: Enterprise Ireland
European Commission Horizon 2020
Health Research Board
Irish Research Council
Science Foundation Ireland
Type of material: Journal Article
Publisher: Mary Ann Liebert
Journal: Journal of Ocular Pharmacology and Therapeutics
Volume: 38
Issue: 1
Start page: 33
End page: 42
Copyright (published version): 2022 Mary Ann Liebert
Keywords: Quininib drug seriesOcular angiogenesisCysteinyl leukotriene receptorsZebrafishPhenotype-based drug discovery
DOI: 10.1089/jop.2021.0074
Language: en
Status of Item: Peer reviewed
ISSN: 1557-7732
This item is made available under a Creative Commons License:
Appears in Collections:Conway Institute Research Collection
Biomolecular and Biomedical Science Research Collection
Veterinary Medicine Research Collection

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