Dual Farnesoid X Receptor/Soluble Epoxide Hydrolase Modulators Derived from Zafirlukast.
ChemMedChem
; 15(1): 50-67, 2020 01 07.
Article
em En
| MEDLINE
| ID: mdl-31670489
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 inâ
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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Compostos de Tosil
/
Receptores Citoplasmáticos e Nucleares
/
Epóxido Hidrolases
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article