Site-specific drug release of monomethyl fumarate to treat oxidative stress disorders

IF 33.1 1区生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Nature biotechnology Pub Date : 2024-11-04 DOI:10.1038/s41587-024-02460-4

Thomas D. Avery, Jiahe Li, Dion J. L. Turner, Mohd S. U. Rasheed, Fisher R. Cherry, Damian L. Stachura, Fátima Rivera-Escalera, David M. Ruiz, Michael J. Lacagnina, Caitlyn M. Gaffney, Clarissa Aguilar, Jingxian Yu, Yang Wang, Huan Xie, Dong Liang, Andrew J. Shepherd, Andrew D. Abell, Peter M. Grace

引用次数: 0

Abstract

Treatment of diseases of oxidative stress through activation of the antioxidant nuclear factor E2-related factor 2 (NRF2) is limited by systemic side effects. We chemically functionalize the NRF2 activator monomethyl fumarate to require Baeyer–Villiger oxidation for release of the active drug at sites of oxidative stress. This prodrug reverses chronic pain in mice with reduced side effects and could be applied to other disorders of oxidative stress.

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治疗氧化应激紊乱的富马酸单甲酯的部位特异性药物释放

通过激活抗氧化剂核因子 E2 相关因子 2（NRF2）来治疗氧化应激疾病受到全身副作用的限制。我们对 NRF2 激活剂富马酸单甲酯进行了化学功能化处理，使其在氧化应激部位释放活性药物时需要进行拜耳-维里格氧化反应。这种原药能逆转小鼠的慢性疼痛，且副作用较小，可用于其他氧化应激紊乱。

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

Nature biotechnology 工程技术-生物工程与应用微生物

CiteScore

63.00

自引率

1.70%

发文量

382

审稿时长

3 months

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