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Combined Cardioprotective and Adipocyte Browning Effects Promoted by the Eutomer of Dual sEH/PPARγ Modulator.
- Source :
-
Journal of medicinal chemistry [J Med Chem] 2021 Mar 11; Vol. 64 (5), pp. 2815-2828. Date of Electronic Publication: 2021 Feb 23. - Publication Year :
- 2021
-
Abstract
- The metabolic syndrome (MetS) is a constellation of cardiovascular and metabolic symptoms involving insulin resistance, steatohepatitis, obesity, hypertension, and heart disease, and patients suffering from MetS often require polypharmaceutical treatment. PPARγ agonists are highly effective oral antidiabetics with great potential in MetS, which promote adipocyte browning and insulin sensitization. However, the application of PPARγ agonists in clinics is restricted by potential cardiovascular adverse events. We have previously demonstrated that the racemic dual sEH/PPARγ modulator RB394 ( 3 ) simultaneously improves all risk factors of MetS in vivo. In this study, we identify and characterize the eutomer of 3 . We provide structural rationale for molecular recognition of the eutomer. Furthermore, we could show that the dual sEH/PPARγ modulator is able to promote adipocyte browning and simultaneously exhibits cardioprotective activity which underlines its exciting potential in treatment of MetS.
- Subjects :
- Animals
Benzamides chemical synthesis
Butyrates chemical synthesis
Cardiotonic Agents chemical synthesis
Cell Differentiation drug effects
Enzyme Inhibitors chemical synthesis
Enzyme Inhibitors pharmacology
HEK293 Cells
Humans
Mice, Inbred C57BL
Stereoisomerism
Mice
Adipocytes drug effects
Benzamides pharmacology
Butyrates pharmacology
Cardiotonic Agents pharmacology
Epoxide Hydrolases metabolism
PPAR gamma agonists
Subjects
Details
- Language :
- English
- ISSN :
- 1520-4804
- Volume :
- 64
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 33620196
- Full Text :
- https://doi.org/10.1021/acs.jmedchem.0c02063