Discovery of the first-in-class dual PPARδ/γ partial agonist for the treatment of metabolic syndrome.
Basic Information
ID: ALA4831519
Journal: Eur J Med Chem
Title: Discovery of the first-in-class dual PPARδ/γ partial agonist for the treatment of metabolic syndrome.
Authors: Li Z, Ren Q, Zhou Z, Cai Z, Wang B, Han J, Zhang L.
Abstract: The peroxisome proliferator-activated receptors (PPARs) exert vital function in the regulation of energy metabolism, which were considered as promising targets of metabolic syndrome. Until now, PPARδ/γ dual agonist is rarely reported, and thereby the pharmacologic action of PPARδ/γ dual agonist is still unclear. In this study, we identified a dual PPARδ/γ partial agonist 6 (ZLY06) based on the cyclization strategy of PPARα/δ dual agonist GFT505. ZLY06 revealed excellent pharmacokinetic profiles suitable for oral medication. Moreover, ZLY06 markedly improved glucolipid metabolism without weight gain, and alleviated fatty liver by promoting the β-oxidation of fatty acid and inhibiting hepatic lipogenesis. In contrast, weight gain and hepatic steatosis were observed in Rosiglitazone, a widely used PPARγ full agonist. All of these results indicated that ZLY06 exhibits potential benefits on metabolic syndrome, while no adverse effects related to PPARγ full agonist.
CiteXplore: 34455359
DOI: 10.1016/j.ejmech.2021.113807
Patent ID: ┄