ZDZ-553 is an orally active STAT1 inhibitor with an IC50 value of 0.87 μM. ZDZ-553 modulates STAT1 signaling to affect downstream lipid metabolism and inflammatory pathways. ZDZ-553 attenuates hepatic steatosis in NASH mouse models. ZDZ-553 reduces inflammatory responses in NASH mouse models. ZDZ-553 can be used for the research of nonalcoholic steatohepatitis [1].
In Vivo, ZDZ-553 (30-60 mg/kg; p.o.; daily; 4 weeks) administered orally at 30 and 60 mg/kg for 4 weeks dose-dependently ameliorates hepatic steatosis, liver damage, and inflammation in HF-CDAA-induced NASH mice, with the 60 mg/kg dose showing greater efficacy than the 30 mg/kg dose and the positive control Dios[1].
In Vitro, ZDZ-553 (24 h) potently inhibits STAT1 activity in stable 293T-STAT1/GAS-Luc cells with an IC50 of 0.87 μM and shows no cytotoxicity at concentrations up to 200 μM[1]. ZDZ-553 (0.052 μM; 0, 30, 60, 120 min) has excellent metabolic stability in human, mouse, and rat liver microsomes, with a T1/2 >120 min across all species[1]. ZDZ-553 (0-200 μM; 24 h) exhibits no cytotoxicity in HepG2 cells at concentrations up to 200 μM[1].
References:
[1]. Zhang Z, et al. Design, Synthesis, and Biological Evaluation of Chromone Derivatives as STAT1 Inhibitors for Treatment of Nonalcoholic Steatohepatitis. J Med Chem. 2026 Feb 12;69(3):2509-2538.
In Vivo, ZDZ-553 (30-60 mg/kg; p.o.; daily; 4 weeks) administered orally at 30 and 60 mg/kg for 4 weeks dose-dependently ameliorates hepatic steatosis, liver damage, and inflammation in HF-CDAA-induced NASH mice, with the 60 mg/kg dose showing greater efficacy than the 30 mg/kg dose and the positive control Dios[1].
In Vitro, ZDZ-553 (24 h) potently inhibits STAT1 activity in stable 293T-STAT1/GAS-Luc cells with an IC50 of 0.87 μM and shows no cytotoxicity at concentrations up to 200 μM[1]. ZDZ-553 (0.052 μM; 0, 30, 60, 120 min) has excellent metabolic stability in human, mouse, and rat liver microsomes, with a T1/2 >120 min across all species[1]. ZDZ-553 (0-200 μM; 24 h) exhibits no cytotoxicity in HepG2 cells at concentrations up to 200 μM[1].
References:
[1]. Zhang Z, et al. Design, Synthesis, and Biological Evaluation of Chromone Derivatives as STAT1 Inhibitors for Treatment of Nonalcoholic Steatohepatitis. J Med Chem. 2026 Feb 12;69(3):2509-2538.