Dual Farnesoid X Receptor/Soluble Epoxide Hydrolase Modulators Derived from Zafirlukast
Abstract: The nuclear farnesoid X receptor (FXR) and the enzyme soluble epoxide hydrolase (sEH) are validated molecular targets to treat metabolic disorders such as non‐alcoholic steatohepatitis (NASH). Their simultaneous modulation in vivo has demonstrated a triad of anti‐NASH effects and thus may generate synergistic efficacy. Here we report dual FXR activators/sEH inhibitors derived from the anti‐asthma drug Zafirlukast. Systematic structural optimization of the scaffold has produced favorable dual potency on FXR and sEH while depleting the original cysteinyl leukotriene receptor antagonism of the lead drug. The resulting polypharmacological activity profile holds promise in the treatment of liver‐related metabolic diseases.
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Erschienen in
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Dual Farnesoid X Receptor/Soluble Epoxide Hydrolase Modulators Derived from Zafirlukast ; volume:15 ; number:1 ; year:2020 ; pages:50-67 ; extent:18
ChemMedChem ; 15, Heft 1 (2020), 50-67 (gesamt 18)
- Urheber
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Schierle, Simone
Helmstädter, Moritz
Schmidt, Jurema
Hartmann, Markus
Horz, Maximiliane
Kaiser, Astrid
Weizel, Lilia
Heitel, Pascal
Proschak, Anna
Hernandez‐Olmos, Victor
Proschak, Ewgenij
Merk, Daniel
- DOI
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10.1002/cmdc.201900576
- URN
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urn:nbn:de:101:1-2022062513272386937074
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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15.08.2025, 07:37 MESZ
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Beteiligte
- Schierle, Simone
- Helmstädter, Moritz
- Schmidt, Jurema
- Hartmann, Markus
- Horz, Maximiliane
- Kaiser, Astrid
- Weizel, Lilia
- Heitel, Pascal
- Proschak, Anna
- Hernandez‐Olmos, Victor
- Proschak, Ewgenij
- Merk, Daniel
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