Discovery and Development of the Quininib Series of Ocular Drugs
| Autor: | Niamh Mahon, Kayleigh Slater, Justine O'Brien, Yolanda Alvarez, Alison Reynolds, Breandán Kennedy |
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| Rok vydání: | 2022 |
| Předmět: |
Pharmacology
Receptors Leukotriene Quininib drug series Phenotype-based drug discovery Diabetic Retinopathy Ocular angiogenesis Neovascularization Pathologic Eye Neoplasms Angiogenesis Inhibitors Retinal Neovascularization Ophthalmology Disease Models Animal Phenotype Drug Development Phenols Retinal Diseases Drug Discovery Quinolines Animals Pharmacology (medical) Cysteinyl leukotriene receptors Zebrafish |
| Zdroj: | Journal of Ocular Pharmacology and Therapeutics |
| ISSN: | 1557-7732 |
| Popis: | 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). Enterprise Ireland European Commission Horizon 2020 Health Research Board Irish Research Council Science Foundation Ireland |
| Databáze: | OpenAIRE |
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