Synthesis and Biological Profile of Omaveloxolone: The Cornerstone for Friedreich Ataxia Treatment.

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-10-07 DOI:10.3390/ijms26199747

Massimiliano Cordaro, Giulia Neri, Shoeb Anwar Mohammed Khawja Ansari, Rocco Buccheri, Angela Scala, Anna Piperno

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Abstract

This review provides a comprehensive overview of the therapeutic potential of omaveloxone (OMA) for the treatment of Friedreich's 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-κB (NF-κB), 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.

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奥马维洛酮的合成和生物学特性：弗里德赖希共济失调治疗的基础。

本文综述了奥马维洛酮（OMA）治疗弗里德赖希共济失调（FA）的治疗潜力，并分析了OMA生产的合成策略的历史发展和现状。OMA激活核因子-2-（红细胞-2）相关（Nrf2）途径，在体外和体内，在动物模型和人类中都是如此。Nrf2通路在细胞氧化应激反应中起着至关重要的作用。此外，OMA已被证明可以减轻线粒体功能障碍，恢复氧化还原稳态，下调炎症反应的关键介质核因子-κB （NF-κB）。通过这些机制，OMA有助于FA患者的组织保护和炎症减少。该综述还强调了未来的前景，重点关注通过创新的给药方法重新分析OMA所面临的挑战及其对FA以外疾病的潜在重新定位。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Molecular Sciences 化学-化学综合

自引率

10.70%

发文量

13472

审稿时长

1.7 months

期刊介绍： The International Journal of Molecular Sciences (ISSN 1422-0067) provides an advanced forum for chemistry, molecular physics (chemical physics and physical chemistry) and molecular biology. It publishes research articles, reviews, communications and short notes. Our aim is to encourage scientists to publish their theoretical and experimental results in as much detail as possible. Therefore, there is no restriction on the length of the papers or the number of electronics supplementary files. For articles with computational results, the full experimental details must be provided so that the results can be reproduced. Electronic files regarding the full details of the calculation and experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material (including animated pictures, videos, interactive Excel sheets, software executables and others).