Discovery of sulfonyl benzoic acid derivatives with joint TGR5-agonist and FXR-antagonist activity for myocardial ischemia/reperfusion injury protection
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Le résumé fourni par la source
TGR5 and FXR are key regulators of metabolic homeostasis and cardiovascular health. Since the cardioprotective capacity of TGR5 activation and FXR inhibition has been recognized, dual modulation of these targets offers a promising therapeutic strategy for myocardial ischemia/reperfusion injury. Herein, sulfonyl benzoic acid derivatives were identified as effective bidirectional modulators, with compound E6 emerging as a potent lead compound. E6 demonstrated robust dual-target activity, significantly preserving cardiomyocyte viability and attenuated reactive oxygen specie overproduction in hypoxia/reoxygenation models. Moreover, oral administration of E6 markedly reduced infarct size and improved cardiac contractile function after ischemia/reperfusion in vivo , without inducing gallbladder-related side effects. Notably, E6 demonstrated superior efficacy in restoring systolic function compared to mono-regulators. Transcriptomic analysis and subsequent validation studies suggested that its therapeutic effects are mediated through favorable modulation of inflammatory response, attenuation of apoptosis, and enhanced cardiomyocytes survival. Our findings underscore the therapeutic advantages of dual TGR5/FXR targeting and establish E6 as a promising bifunctional lead compound for the treatment of myocardial ischemia/reperfusion injury.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Discovery of sulfonyl benzoic acid derivatives with joint TGR5-agonist and FXR-antagonist activity for myocardial ischemia/reperfusion injury protection
- Date Crossref
- 01/06/2026
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Peking University Department of Cardiology and Institute of Vascular Medicine pays non établi dans la noticeUniversité ou école supérieure
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Shandong University pays non établi dans la noticeUniversité ou école supérieure
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Chinese Academy of Medical Sciences & Peking Union Medical College pays non établi dans la noticeUniversité ou école supérieure
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State Key Laboratory of Synthetic Chemistry pays non établi dans la noticeStructure de recherche
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Innovation and Technology Commission pays non établi dans la noticeOrganisme public
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School of Pharmaceutical Sciences State Key Laboratory of Natural and Biomimetic Drugs pays non établi dans la noticeUniversité ou école supérieure
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School of Basic Medical Sciences Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology pays non établi dans la noticeUniversité ou école supérieure
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Research Unit of Medical Science Research Management/Basic and Clinical Research of Metabolic Cardiovascular Diseases pays non établi dans la noticeStructure de recherche
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Laboratory for Synthetic Chemistry and Chemical Biology Limited pays non établi dans la noticeStructure de recherche
Department of Cardiology and Institute of Vascular Medicine — Peking University, Shandong University et Chinese Academy of Medical Sciences & Peking Union Medical College, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.