Design and discovery of soluble epoxide hydrolase inhibitors for the treatment of cardiovascular diseases
| العنوان: | Design and discovery of soluble epoxide hydrolase inhibitors for the treatment of cardiovascular diseases |
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| المؤلفون: | Clothilde Roche, Jeremy Bellien, Thomas Duflot, Dominique Guerrot, Fabien Lamoureux |
| المصدر: | Expert Opinion on Drug Discovery. 9:229-243 |
| بيانات النشر: | Informa Healthcare, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Epoxide Hydrolases, chemistry.chemical_classification, Epoxide hydrolase 2, Endothelium, Drug discovery, Cytochrome P450, Pharmacology, Biology, medicine.disease, chemistry.chemical_compound, Enzyme, medicine.anatomical_structure, Metabolic Diseases, chemistry, Cardiovascular Diseases, Drug Discovery, cardiovascular system, medicine, biology.protein, Animals, Eicosanoids, Humans, Arachidonic acid, Endothelial dysfunction |
| الوصف: | Cardiovascular diseases are a leading cause of death in developed countries. Increasing evidence shows that the alteration in the normal functions of the vascular endothelium plays a major role in the development of cardiovascular diseases. However, specific agents designed to prevent endothelial dysfunction and related cardiovascular complications are still lacking. One emerging strategy is to increase the bioavailability of epoxyeicosatrienoic acids (EETs), synthesized by cytochrome P450 epoxygenases from arachidonic acid. EETs are endothelium-derived hyperpolarising and relaxing factors and display attractive anti-inflammatory and metabolic properties. Genetic polymorphism studies in humans, and experiments in animal models of diseases, have identified soluble epoxide hydrolase (sEH), the major enzyme involved in EET degradation, as a potential pharmacological target.This review presents EET pathway and its functions and summarises the data supporting the development of sEH inhibitors for the treatment of cardiovascular and metabolic diseases. Furthermore, the authors present the different chemical families of sEH inhibitors developed and their effects in animal models of cardiovascular and metabolic diseases.Several generations of sEH inhibitors have now been designed to treat endothelial dysfunction and cardiovascular complications for a variety of diseases. The safety of these drugs remains to be carefully investigated, particularly in relation to carcinogenesis. The increasing knowledge of the biological role of each of the EET isomers and of their metabolites may improve their pharmacological profile. This, in turn, could potentially lead to the identification of new pharmacological agents that achieve the cellular effects needed without the deleterious side effects. |
| تدمد: | 1746-045X 1746-0441 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a8bc477a45d80079c6caf18c8f75a9a4Test https://doi.org/10.1517/17460441.2014.881354Test |
| رقم الانضمام: | edsair.doi.dedup.....a8bc477a45d80079c6caf18c8f75a9a4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1746045X 17460441 |
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