Dual farnesoid X receptor/soluble epoxide hydrolase modulators derived from Zafirlukast

  • 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.

Download full text files

Export metadata

Additional Services

Share in Twitter Search Google Scholar
Metadaten
Author:Simone Schierle, Moritz Helmstädter, Jurema Schmidt, Markus Hartmann, Maximiliane Horz, Astrid Kaiser, Lilia Weizel, Pascal Heitel, Anna Proschak, Victor Hernandez‐Olmos, Ewgenij Proschak, Daniel MerkORCiDGND
URN:urn:nbn:de:hebis:30:3-570413
DOI:https://doi.org/10.1002/cmdc.201900576
ISSN:1860-7187
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/31670489
Parent Title (German):ChemMedChem
Publisher:Wiley-VCH
Place of publication:Weinheim
Document Type:Article
Language:English
Date of Publication (online):2019/10/31
Date of first Publication:2019/10/31
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2020/12/10
Tag:NAFLD; NASH; Polypharmacology; non-alcoholic steatohepatitis; nuclear receptor
Volume:15.2020
Issue:1
Page Number:18
First Page:50
Last Page:67
HeBIS-PPN:477031897
Institutes:Biochemie, Chemie und Pharmazie / Biochemie und Chemie
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften
5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
Licence (English):License LogoCreative Commons - Namensnennung-Nicht kommerziell 4.0