{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T22:53:47Z","timestamp":1793141627451,"version":"4.5.0"},"reference-count":67,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Progetto Pharma-HUB-Hub per il riposizionamento di farmaci nelle malattie rare del sistema nervoso in et\u00e0 pediatrica","award":["CUP J43C22000500006-T4-AN-04"],"award-info":[{"award-number":["CUP J43C22000500006-T4-AN-04"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This review provides a comprehensive overview of the therapeutic potential of omaveloxone (OMA) for the treatment of Friedreich\u2019s ataxia (FA), along with an analysis of the historical development and current status of the synthetic strategies for OMA production. OMA activates the nuclear factor-2-(erythroid-2)-related (Nrf2) pathway in vitro and in vivo, in both animal models and humans. The Nrf2 pathway plays a crucial role in the cellular response to oxidative stress. Furthermore, OMA has been shown to mitigate mitochondrial dysfunction, restore redox homeostasis and downregulate nuclear factor-\u03baB (NF-\u03baB), a key mediator of inflammatory responses. Through these mechanisms, OMA contributes to tissue protection and inflammation reduction in patients with FA. The review also highlights future perspective, focusing on the challenges associated with OMA reprofiling through innovative drug delivery approaches and its potential repurposing for diseases beyond FA.<\/jats:p>","DOI":"10.3390\/ijms26199747","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T10:48:07Z","timestamp":1759834087000},"page":"9747","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Synthesis and Biological Profile of Omaveloxolone: The Cornerstone for Friedreich Ataxia Treatment"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8637-3999","authenticated-orcid":false,"given":"Massimiliano","family":"Cordaro","sequence":"first","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, 31 V.le F. Stagno D\u2019Alcontres, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4458-0022","authenticated-orcid":false,"given":"Giulia","family":"Neri","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, 31 V.le F. Stagno D\u2019Alcontres, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2882-3573","authenticated-orcid":false,"given":"Shoeb Anwar Mohammed Khawja","family":"Ansari","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, 31 V.le F. Stagno D\u2019Alcontres, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8966-0439","authenticated-orcid":false,"given":"Rocco","family":"Buccheri","sequence":"additional","affiliation":[{"name":"Department of Drug Sciences, University of Catania, V.le A. Doria, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2171-9033","authenticated-orcid":false,"given":"Angela","family":"Scala","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, 31 V.le F. Stagno D\u2019Alcontres, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6004-5196","authenticated-orcid":false,"given":"Anna","family":"Piperno","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, 31 V.le F. Stagno D\u2019Alcontres, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7092151","DOI":"10.1155\/2019\/7092151","article-title":"Vascular Inflammation and Oxidative Stress: Major Triggers for Cardiovascular Disease","volume":"2019","author":"Steven","year":"2019","journal-title":"Oxidative Med. Cell. 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