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- W3003622217 abstract "In the effort to identify anti-diabetic drug, we discovered a novel free fatty acid receptor 1 (FFA1) agonist CPU025, which is structurally different from previously reported FFA1 agonists. The present study revealed CPU025 is a potent FFA1 agonist (EC50 = 38.7 nM) with moderate agonistic activity on PPARδ (EC50 = 625.6 nM), and promotes insulin secretion at a glucose-dependent manner. Modeling study also illuminated CPU025 forms interaction with key residues closely related to the agonistic effects of FFA1 and PPARδ. Long-term treatment of CPU025 exerted better glycemic control and lipid profile than TAK-875, the most advanced FFA1 partial agonist in this field. Moreover, CPU025 improved β-cell function and alleviated fatty liver in ob/ob mice. Further study suggested CPU025 could alleviate fatty liver through regulating the expression of genes involved in fatty acid β-oxidation, lipoprotein lipolysis, lipid synthesis, oxidative stress and mitochondrial function. These results indicate that long-term treatment of CPU025 improves glucose and lipid metabolism, and may be useful for the treatment of diabetes mellitus and fatty liver." @default.
- W3003622217 created "2020-02-07" @default.
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- W3003622217 date "2020-03-01" @default.
- W3003622217 modified "2023-10-09" @default.
- W3003622217 title "A novel FFA1 agonist, CPU025, improves glucose-lipid metabolism and alleviates fatty liver in obese-diabetic (ob/ob) mice" @default.
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- W3003622217 doi "https://doi.org/10.1016/j.phrs.2020.104679" @default.
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