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.

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch

References and Relationships

• Bibliographic citation: 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)

Contributors, Places and Time

• Creator: 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

Further information

• DOI: 10.1002/cmdc.201900576
• URN: urn:nbn:de:101:1-2022062513272386937074
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 15.08.2025, 7:37 AM CEST