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

doi:10.1038/s41587-024-02460-4

. 2024 Nov 4.

doi: 10.1038/s41587-024-02460-4. Online ahead of print.

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

Thomas D Avery^#^{1

2

3}, Jiahe Li^#^{4

5}, Dion J L Turner^#^{1

2

3}, Mohd S U Rasheed^{4

5}, Fisher R Cherry^{4

5}, Damian L Stachura^{1

2

3}, Fátima Rivera-Escalera^{4

5}, David M Ruiz^{4

5}, Michael J Lacagnina^{4

5}, Caitlyn M Gaffney^{4

5}, Clarissa Aguilar^{4

5}, Jingxian Yu^{1

2

3}, Yang Wang⁶, Huan Xie⁶, Dong Liang⁶, Andrew J Shepherd^{4

5}, Andrew D Abell^{7

8

9}, Peter M Grace^{10

11}

Affiliations

¹ ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), The University of Adelaide, Adelaide, South Australia, Australia.
² Institute for Photonics and Advanced Sensing (IPAS), The University of Adelaide, Adelaide, South Australia, Australia.
³ Department of Chemistry, The University of Adelaide, Adelaide, South Australia, Australia.
⁴ Laboratories of Neuroimmunology, Department of Symptom Research, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁵ MD Anderson Pain Research Consortium, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁶ Department of Pharmaceutical Science, Texas Southern University, Houston, TX, USA.
⁷ ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), The University of Adelaide, Adelaide, South Australia, Australia. andrew.abell@adelaide.edu.au.
⁸ Institute for Photonics and Advanced Sensing (IPAS), The University of Adelaide, Adelaide, South Australia, Australia. andrew.abell@adelaide.edu.au.
⁹ Department of Chemistry, The University of Adelaide, Adelaide, South Australia, Australia. andrew.abell@adelaide.edu.au.
¹⁰ Laboratories of Neuroimmunology, Department of Symptom Research, University of Texas MD Anderson Cancer Center, Houston, TX, USA. pgrace@mdanderson.org.
¹¹ MD Anderson Pain Research Consortium, University of Texas MD Anderson Cancer Center, Houston, TX, USA. pgrace@mdanderson.org.

^# Contributed equally.

PMID: 39496929
DOI: 10.1038/s41587-024-02460-4

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

Thomas D Avery et al. Nat Biotechnol. 2024.

. 2024 Nov 4.

doi: 10.1038/s41587-024-02460-4. Online ahead of print.

Authors

Affiliations

¹ ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), The University of Adelaide, Adelaide, South Australia, Australia.
² Institute for Photonics and Advanced Sensing (IPAS), The University of Adelaide, Adelaide, South Australia, Australia.
³ Department of Chemistry, The University of Adelaide, Adelaide, South Australia, Australia.
⁴ Laboratories of Neuroimmunology, Department of Symptom Research, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁵ MD Anderson Pain Research Consortium, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁶ Department of Pharmaceutical Science, Texas Southern University, Houston, TX, USA.
⁷ ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), The University of Adelaide, Adelaide, South Australia, Australia. andrew.abell@adelaide.edu.au.
⁸ Institute for Photonics and Advanced Sensing (IPAS), The University of Adelaide, Adelaide, South Australia, Australia. andrew.abell@adelaide.edu.au.
⁹ Department of Chemistry, The University of Adelaide, Adelaide, South Australia, Australia. andrew.abell@adelaide.edu.au.
¹⁰ Laboratories of Neuroimmunology, Department of Symptom Research, University of Texas MD Anderson Cancer Center, Houston, TX, USA. pgrace@mdanderson.org.
¹¹ MD Anderson Pain Research Consortium, University of Texas MD Anderson Cancer Center, Houston, TX, USA. pgrace@mdanderson.org.

^# Contributed equally.

PMID: 39496929
DOI: 10.1038/s41587-024-02460-4

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.

PubMed Disclaimer

References

1. GBD Diseases and Injuries Collaborators. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet 396, 1204–1222 (2020). - DOI
1. Dodson, M. et al. Modulating NRF2 in disease: timing is everything. Annu. Rev. Pharmacol. Toxicol. 59, 555–575 (2019). - PubMed - DOI
1. Cuadrado, A. et al. Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases. Nat. Rev. Drug Discov. 18, 295–317 (2019). - PubMed - DOI
1. Forman, H. J. & Zhang, H. Targeting oxidative stress in disease: promise and limitations of antioxidant therapy. Nat. Rev. Drug Discov. 20, 689–709 (2021). - PubMed - PMC - DOI
1. Hoogendoorn, A. et al. Emerging therapeutic applications for fumarates. Trends Pharmacol. Sci. 42, 239–254 (2021). - PubMed - PMC - DOI

Grants and funding

LinkOut - more resources

Full Text Sources
- Nature Publishing Group

[1] GBD Diseases and Injuries Collaborators. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet 396, 1204–1222 (2020). - DOI

[2] GBD Diseases and Injuries Collaborators. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet 396, 1204–1222 (2020). - DOI

[3] Dodson, M. et al. Modulating NRF2 in disease: timing is everything. Annu. Rev. Pharmacol. Toxicol. 59, 555–575 (2019). - PubMed - DOI

[4] Dodson, M. et al. Modulating NRF2 in disease: timing is everything. Annu. Rev. Pharmacol. Toxicol. 59, 555–575 (2019). - PubMed - DOI

[5] Cuadrado, A. et al. Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases. Nat. Rev. Drug Discov. 18, 295–317 (2019). - PubMed - DOI

[6] Cuadrado, A. et al. Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases. Nat. Rev. Drug Discov. 18, 295–317 (2019). - PubMed - DOI

[7] Forman, H. J. & Zhang, H. Targeting oxidative stress in disease: promise and limitations of antioxidant therapy. Nat. Rev. Drug Discov. 20, 689–709 (2021). - PubMed - PMC - DOI

[8] Forman, H. J. & Zhang, H. Targeting oxidative stress in disease: promise and limitations of antioxidant therapy. Nat. Rev. Drug Discov. 20, 689–709 (2021). - PubMed - PMC - DOI

[9] Hoogendoorn, A. et al. Emerging therapeutic applications for fumarates. Trends Pharmacol. Sci. 42, 239–254 (2021). - PubMed - PMC - DOI

[10] Hoogendoorn, A. et al. Emerging therapeutic applications for fumarates. Trends Pharmacol. Sci. 42, 239–254 (2021). - PubMed - PMC - DOI

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Abstract

Similar articles

References

Grants and funding

LinkOut - more resources

Full Text Sources

Abstract

Similar articles

References

Related information

Grants and funding

LinkOut - more resources

Full Text Sources