{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:01:58Z","timestamp":1787022118696,"version":"build-2736575974"},"reference-count":83,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T00:00:00Z","timestamp":1670803200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Drug repurposing has been shown to bring safe medications to new patient populations, as recently evidenced by the COVID-19 pandemic. We investigated whether we could use phenotypic screening to repurpose drugs for the treatment of Peyronie\u2019s disease (PD). PD is a fibrotic disease characterised by continued myofibroblast presence and activity leading to formation of a plaque in the penile tunica albuginea (TA) that can cause pain during erection, erectile dysfunction, and penile deformity. PD affects 3\u20139% of men with treatment options limited to surgery or injection of collagenase which can only be utilised at late stages after the plaque is formed. Currently there are no approved medications that can be offered to patients presenting with early disease before the formation of the plaque. Drug repurposing may therefore be the ideal strategy to identify medical treatments to address this unmet medical need in early PD. We used primary human fibroblasts from PD patients in a phenotypic screening assay that measures TGF-\u03b21-induced myofibroblast transformation which is the main cellular phenotype that drives the pathology in early PD. A library of FDA-approved 1,953 drugs was screened in duplicate wells at a single concentration (10 \u03bcM) in presence of TGF-\u03b21. The myofibroblast marker \u03b1-SMA was quantified after 72h incubation. A positive control of SB-505124 (TGF-\u03b21 receptor antagonist) was included on each plate. Hits were defined as showing &gt;80% inhibition, whilst retaining &gt;80% cell viability. 26 hits (1.3%) were identified which were divided into the following main groups: anti-cancer drugs, anti-inflammation, neurology, endocrinology, and imaging agents. Five of the top-ten drugs that increase myofibroblast-transformation appear to act on VEGFR. This is the first phenotypic screening of FDA-approved drugs for PD and our results suggest that it is a viable method to predict drugs with potential for repurposing to treat early PD.<\/jats:p>","DOI":"10.1371\/journal.pone.0277646","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T13:24:52Z","timestamp":1670851492000},"page":"e0277646","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Phenotypic screening of 1,953 FDA-approved drugs reveals 26 hits with potential for repurposing for Peyronie\u2019s disease"],"prefix":"10.1371","volume":"17","author":[{"given":"Marcus M.","family":"Ilg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice R.","family":"Lapthorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Ralph","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4856-285X","authenticated-orcid":true,"given":"Selim","family":"Cellek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,12,12]]},"reference":[{"key":"pone.0277646.ref001","first-page":"693","article-title":"Dexamethasone in Hospitalized Patients with Covid-19","volume":"384","year":"2020","journal-title":"N Engl J Med"},{"key":"pone.0277646.ref002","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1056\/NEJMoa2028700","article-title":"Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia","volume":"384","author":"IO Rosas","year":"2021","journal-title":"N Engl J Med"},{"key":"pone.0277646.ref003","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/448645a","article-title":"New uses for old drugs","volume":"448","author":"CR Chong","year":"2007","journal-title":"Nature"},{"key":"pone.0277646.ref004","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.3389\/fphar.2020.588654","article-title":"Challenges for Drug Repurposing in the COVID-19 Pandemic Era","volume":"11","author":"J Sultana","year":"2020","journal-title":"Front Pharmacol"},{"key":"pone.0277646.ref005","doi-asserted-by":"crossref","first-page":"208","DOI":"10.3389\/fonc.2021.627229","article-title":"New Approaches in Oncology for Repositioning Drugs: The Case of PDE5 Inhibitor Sildenafil","volume":"11","author":"M Cruz-Burgos","year":"2021","journal-title":"Front Oncol"},{"key":"pone.0277646.ref006","unstructured":"Walton S, Schumock G, Lee K-V, Alexander G, Meltzer D, Stafford R. eveloping evidence-based research priorities for off-label drug use. 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