ZLY28 is the first-in-class intestinal restricted and orally active FXR and FABP1 dual modulator. ZLY28 also is a novel anti-NASH agent. ZLY28 can be used for the research of nonalcoholic steatohepatitis (NASH)[1].
in vivo
ZLY28 (oral; 20 mg/kg) significantly alleviates fatty liver by regulating multiple pathogeneses, including lipid metabolism, inflammation, oxidative stress, and fibrosis in the NASH mice model[1].
Animal Model:
8 weeks old male C57BL/6 mice[1]
Dosage:
20 mg/kg
Administration:
Oral administration
Result:
Mainly distributed in the ileum with an ileum/plasma ratio of 104.1.
Significantly alleviated hepatic steatosis, lobular inflammation and ballooning.
Improved hepatic lipid homeostasis by inhibiting lipogenesis and promoting lipolysis.
Downregulated the gene expression levels.
Exhibited an acceptable safety profile with no acute toxicity.
References
[1] Ren Q, et al. Discovery of the First-in-Class Intestinal Restricted FXR and FABP1 Dual Modulator ZLY28 for the Treatment of Nonalcoholic Fatty Liver Disease. J Med Chem. 2023;66(9):6082-6104. DOI:10.1021/acs.jmedchem.2c01918
