ZG-2305 is a potent, and selective inhibitor of factor inhibiting HIF (FIH) with Ki of 79.6 nM, 38-fold selectivity over HIF prolyl hydroxylase PHD2.
ZG-2305 strongly regulatesFIH-dependent HIF target gene EGLN3 in Hep3B cells, but not the HIF-1α regulated BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) gene, the primarily HIF-2α regulated erythropoietin (EPO) gene, or the HIF-1α and HIF-2α regulated glucose transporter 1 (SLC2A1) gene.
ZG-2305 dose-dependently reduces lipid accumulation in 3T3-L1 derived adipocytes.
ZG-2305 (50 mg/kg) improves western-diet induced obesity and obesity-related symptoms in western-diet-induced obesity mice, dose-dependently reduces the hepatic TG content and significantly reduces the hepatic TC level.
ZG-2305 ameliorates nonalcoholic steatohepatitis (NASH) related pathological phenotypes in the HF-CDAA-diet induced NASH mouse model.