1. JAK/STAT Signaling Stem Cell/Wnt
  2. STAT
  3. ZDZ-553

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.

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ZDZ-553

ZDZ-553 Chemical Structure

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Description

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].

IC50 & Target[1]

STAT1

0.87 μM (IC50)

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Cytotoxicity Assay[1]

Cell Line: HepG2 cells
Concentration: 0-200 μM (serial 2-fold dilutions starting at 200 μM)
Incubation Time: 24 h
Result: Showed no cytotoxicity after 24 h of exposure, with no decrease in cell viability even at the highest tested concentration of 200 μM.
Parmacokinetics
Species Dose Route AUC0-inf Cmax T1/2 MRT0-inf Tmax F
Rat[1] 30 mg/kg i.v. 69,512 ng·h/mL 2467 ng/mL 16.63 h 24.3 h / /
Rat[1] 30 mg/kg p.o. 12,599 ng·h/mL 819 ng/mL 12.18 h 18.8 h 1.13 h 18.1 %
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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: C57BL/6J (male, 7−8 weeks old, 20-23 g, HF-CDAA diet-induced)[1]
Dosage: 30 mg/kg; 60 mg/kg
Administration: p.o.; daily; 4 weeks
Result: Reduced hepatic triglyceride (TG) and total cholesterol (TC) levels, reduced serum ALT and AST levels; reduced mRNA expression of hepatic acetyl-CoA carboxylase (ACC), fatty acid synthase (FASN), FATP-1, IL-6, IL-1β, TNF-α, and CXCL10; decreased NAFLD Activity Score (NAS) compared to vehicle controls; reduced hepatocellular ballooning (H&E staining) and reduced size/quantity of lipid droplets (Oil Red O staining) at 30 mg/kg.
Produced greater dose-dependent reductions in hepatic TG, TC, serum AST, and mRNA expression of ACC, FASN, FATP-1, IL-6, IL-1β, TNF-α, and CXCL10 compared to the 30 mg/kg dose; resulted in a larger decrease in NAS compared to the 30 mg/kg dose; showed more pronounced improvements in hepatocellular ballooning and lipid droplet accumulation (histological staining) compared to the 30 mg/kg dose at 60 mg/kg.
Showed more significant reductions in hepatic TG, TC, serum AST, and inflammatory cytokine mRNA expression than the positive control Dios at 60 mg/kg at both doses.
Molecular Weight

404.26

Formula

C18H10F6O4

Appearance

Solid

Color

Off-white to light yellow

SMILES

COC1=C2C(C=C(OC2=CC(O)=C1)C3=CC(C(F)(F)F)=CC(C(F)(F)F)=C3)=O

Shipping

Room temperature in continental US; may vary elsewhere.

Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : 83.33 mg/mL (206.13 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.4737 mL 12.3683 mL 24.7366 mL
5 mM 0.4947 mL 2.4737 mL 4.9473 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

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In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

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Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Calculation results:
Working solution concentration: mg/mL
Purity & Documentation

Purity: 99.91%

References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 2.4737 mL 12.3683 mL 24.7366 mL 61.8414 mL
5 mM 0.4947 mL 2.4737 mL 4.9473 mL 12.3683 mL
10 mM 0.2474 mL 1.2368 mL 2.4737 mL 6.1841 mL
15 mM 0.1649 mL 0.8246 mL 1.6491 mL 4.1228 mL
20 mM 0.1237 mL 0.6184 mL 1.2368 mL 3.0921 mL
25 mM 0.0989 mL 0.4947 mL 0.9895 mL 2.4737 mL
30 mM 0.0825 mL 0.4123 mL 0.8246 mL 2.0614 mL
40 mM 0.0618 mL 0.3092 mL 0.6184 mL 1.5460 mL
50 mM 0.0495 mL 0.2474 mL 0.4947 mL 1.2368 mL
60 mM 0.0412 mL 0.2061 mL 0.4123 mL 1.0307 mL
80 mM 0.0309 mL 0.1546 mL 0.3092 mL 0.7730 mL
100 mM 0.0247 mL 0.1237 mL 0.2474 mL 0.6184 mL
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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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Product Name:
ZDZ-553
Cat. No.:
HY-181792
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