Site-Specific Drug Release of Monomethyl Fumarate to Treat Oxidative Stress Disorders

Authors

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

Language

English

Publication Date

10-1-2025

Journal

Nature Biotechnology

DOI

10.1038/s41587-024-02460-4

PMID

39496929

PMCID

PMC12049564

PubMedCentral® Posted Date

11-4-2024

PubMedCentral® Full Text Version

Post-print

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.

Keywords

Oxidative Stress, Animals, Mice, NF-E2-Related Factor 2, Fumarates, Humans, Prodrugs, Drug Liberation, Chronic Pain, Maleates, Drug discovery and development, Chronic pain, Small molecules

Published Open-Access

yes

Recommended Citation

Avery, Thomas D; Li, Jiahe; Turner, Dion J L; et al., "Site-Specific Drug Release of Monomethyl Fumarate to Treat Oxidative Stress Disorders" (2025). Faculty, Staff and Student Publications. 5776.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5776