Dimethoxybenzohomoadamantane-based soluble epoxide hydrolase inhibitors: <i>in vivo</i> efficacy in a murine model of chemotherapy-induced neuropathic pain
The soluble epoxide hydrolase (sEH) has recently emerged as a promising target for the treatment of several pain-related conditions. Herein, we report the design and synthesis of a peripherally restricted sEH inhibitor with high potency and good Drug Metabolism and Pharmacokinetics (DMPK) properties. Molecular dynamics and X-ray crystallography helped reveal the binding of these inhibitors to sEH. The selected compound showed a robust analgesic effect in a dose-dependent manner in a murine model of chemotherapy-induced neuropathic pain (CINP). Moreover, the compound also prevented the development of paclitaxel-induced neuropathic pain. Overall, these results suggest that peripheral inhibition of sEH might constitute a novel therapy to prevent and treat CINP.
Authors
- Beatrice Jora (ORCID: https://orcid.org/0000-0002-0030-2450)
- Filippo Prischi (ORCID: https://orcid.org/0000-0003-2107-938X)
- Qiongju Qiu (ORCID: https://orcid.org/0000-0001-9022-3651)
- Sílvia Osuna (ORCID: https://orcid.org/0000-0003-3657-6469)
- Coral Sanfeliu (ORCID: https://orcid.org/0000-0002-9004-1206)
- Sandra Codony (ORCID: https://orcid.org/0000-0003-0539-673X)
- Andrea Bertran‐Mostazo (ORCID: https://orcid.org/0000-0002-7971-6540)
- Christophe Morisseau (ORCID: https://orcid.org/0000-0002-5672-6631)
- Clara Bartra (ORCID: https://orcid.org/0000-0001-7426-0751)
- Bruce D. Hammock (ORCID: https://orcid.org/0000-0003-1408-8317)
- Santiago Vázquez (ORCID: https://orcid.org/0000-0002-9296-6026)
- Andreea L. Turcu (ORCID: https://orcid.org/0000-0001-9732-2249)
- Maria R. Conte (ORCID: https://orcid.org/0000-0001-8558-2051)
- Ferran Feixas (ORCID: https://orcid.org/0000-0001-5147-0000)
- Christian Griñán‐Ferré (ORCID: https://orcid.org/0000-0002-5424-9130)
- Belén Pérez (ORCID: https://orcid.org/0000-0001-5801-1704)
- Miriam Santos-Caballero (ORCID: https://orcid.org/0000-0002-5713-4136)
- Jose Manuel Brea (ORCID: https://orcid.org/0000-0002-5523-1979)
- Rubén Corpas (ORCID: https://orcid.org/0000-0002-7051-1493)
- Marı́a Isabel Loza (ORCID: https://orcid.org/0000-0003-4730-0863)
- Carla Calvó‐Tusell (ORCID: https://orcid.org/0000-0003-2681-8460)
- Mercè Pallàs (ORCID: https://orcid.org/0000-0003-3095-4254)
- Cristina Val (ORCID: https://orcid.org/0009-0001-8761-8545)
- Carles Galdeano
- Celia Escriche (ORCID: https://orcid.org/0009-0004-2968-7341)
- Enrique J. Cobos (ORCID: https://orcid.org/0000-0003-1308-6264)
Institutions
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Universitat Autònoma de Barcelona (ES)
- King's College London (GB)
- Universitat de Girona (ES)
- Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
- Center for Research in Molecular Medicine and Chronic Diseases (ES)
- Instituto de Investigación Biosanitaria de Granada (ES)
- Institut d'Investigacions Biomèdiques de Barcelona (ES)
- Instituto de Química y Fisicoquímica Biológicas (AR)
- Sylvester Comprehensive Cancer Center (US)
- Institute of Pharmacology (CZ)
- Universitat de Barcelona (ES)
- University of California, Davis (US)
Publication Details
- Journal
- Journal of Enzyme Inhibition and Medicinal Chemistry
- Published
- 2025-10-23
- DOI
- https://doi.org/10.1080/14756366.2025.2574990
- Citations
- 1
- Primary Topic
- Eicosanoids and Hypertension Pharmacology
- Type
- article
- Field-Weighted Citation Impact
- 1.11