{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:56:41Z","timestamp":1790805401834,"version":"4.1.0"},"reference-count":60,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T00:00:00Z","timestamp":1681948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In this paper, we present the development of a computer-based repurposing approach to identify FDA-approved drugs that are potentially able to interfere with irisin dimerization. It has been established that altered levels of irisin dimers are a pure hallmark of lipodystrophy (LD) syndromes. Accordingly, the identification of compounds capable of slowing down or precluding the irisin dimers\u2019 formation could represent a valuable therapeutic strategy in LD. Combining several computational techniques, we identified five FDA-approved drugs with satisfactory computational scores (iohexol, XP score = \u22127.70 kcal\/mol, SP score = \u22125.5 kcal\/mol, \u0394Gbind = \u221261.47 kcal\/mol, \u0394Gbind (average) = \u221260.71 kcal\/mol; paromomycin, XP score = \u22127.23 kcal\/mol, SP score = \u22126.18 kcal\/mol, \u0394Gbind = \u221250.14 kcal\/mol, \u0394Gbind (average) = \u221249.13 kcal\/mol; zoledronate, XP score = \u22126.33 kcal\/mol, SP score = \u22125.53 kcal\/mol, \u0394Gbind = \u221232.38 kcal\/mol, \u0394Gbind (average) = \u221229.42 kcal\/mol; setmelanotide, XP score = \u22126.10 kcal\/mol, SP score = \u22127.24 kcal\/mol, \u0394Gbind = \u221256.87 kcal\/mol, \u0394Gbind (average) = \u221262.41 kcal\/mol; and theophylline, XP score = \u22125.17 kcal\/mol, SP score = \u22125.55 kcal\/mol, \u0394Gbind = \u221233.25 kcal\/mol, \u0394Gbind (average) = \u221235.29 kcal\/mol) that are potentially able to disrupt the dimerization of irisin. For this reason, they deserve further investigation to characterize them as irisin disruptors. Remarkably, the identification of drugs targeting this process can offer novel therapeutic opportunities for the treatment of LD. Furthermore, the identified drugs could provide a starting point for a repositioning approach, synthesizing novel analogs with improved efficacy and selectivity against the irisin dimerization process.<\/jats:p>","DOI":"10.3390\/ijms24087578","type":"journal-article","created":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T05:35:46Z","timestamp":1681968946000},"page":"7578","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Disruption of Irisin Dimerization by FDA-Approved Drugs: A Computational Repurposing Approach for the Potential Treatment of Lipodystrophy Syndromes"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7899-0954","authenticated-orcid":false,"given":"Lorenzo","family":"Flori","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9375-6242","authenticated-orcid":false,"given":"Simone","family":"Brogi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy"},{"name":"Bioinformatics Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4311-9952","authenticated-orcid":false,"given":"Hajar","family":"Sirous","sequence":"additional","affiliation":[{"name":"Bioinformatics Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Calderone","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4500","DOI":"10.1210\/jc.2016-2466","article-title":"The Diagnosis and Management of Lipodystrophy Syndromes: A Multi-Society Practice Guideline","volume":"101","author":"Brown","year":"2016","journal-title":"J. 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