Dimethoxybenzohomoadamantane-based soluble epoxide hydrolase inhibitors: in vivo efficacy in a murine model of chemotherapy-induced neuropathic pain [Dataset]
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...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | conjunto de datos |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:dnet:digitalcsic_::756eff34b5884d1c29ad84dd2da787c5 |
| Acceso en línea: | http://hdl.handle.net/10261/419746 https://digital.csic.es/handle/10261/419739 |
| Access Level: | acceso abierto |
| Palabra clave: | Benzohomoadamantane Chemotherapy-induced neuropathic pain Epoxyeicosatrienoic acids Soluble epoxide hydrolase Urea |
| Sumario: | 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. |
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