Site-specific drug release of monomethyl fumarate to treat oxidative stress disorders
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.
Authors
- Clarissa Aguilar
- Huan Xie (ORCID: https://orcid.org/0000-0002-0591-5619)
- Jingxian Yu (ORCID: https://orcid.org/0000-0002-6489-5988)
- Michael J. Lacagnina (ORCID: https://orcid.org/0000-0003-2468-2467)
- Caitlyn M. Gaffney
- Mohd Sami Ur Rasheed (ORCID: https://orcid.org/0000-0002-7521-2919)
- Andrew J. Shepherd (ORCID: https://orcid.org/0000-0002-8440-6192)
- Andrew D. Abell (ORCID: https://orcid.org/0000-0002-0604-2629)
- Fisher R. Cherry (ORCID: https://orcid.org/0009-0001-7646-8422)
- Damian L. Stachura (ORCID: https://orcid.org/0000-0002-4895-1062)
- Dion J. L. Turner (ORCID: https://orcid.org/0000-0002-5503-6380)
- Thomas D. Avery (ORCID: https://orcid.org/0000-0001-6882-5461)
- Peter M. Grace (ORCID: https://orcid.org/0000-0002-8999-1220)
- Yang Wang (ORCID: https://orcid.org/0000-0002-5941-5740)
- Jiahe Li (ORCID: https://orcid.org/0000-0001-8496-4787)
- David Ruiz
- Liang Dong (ORCID: https://orcid.org/0000-0003-0286-9001)
- Fátima Rivera-Escalera
Institutions
- The University of Texas MD Anderson Cancer Center (US)
- Texas Southern University (US)
- The University of Adelaide (AU)
Publication Details
- Journal
- Nature Biotechnology
- Published
- 2024-11-04
- DOI
- https://doi.org/10.1038/s41587-024-02460-4
- Citations
- 12
- Primary Topic
- Pharmacological Effects of Natural Compounds
- Type
- article
- Field-Weighted Citation Impact
- 5.60
Funders
- Cancer Prevention and Research Institute of Texas
- National Institutes of Health
- University of Texas MD Anderson Cancer Center
- Australian Research Council
- National Institute of Neurological Disorders and Stroke