| Size | Price | Stock | Qty |
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| 500mg |
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| 1g |
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| Other Sizes |
| Targets |
Ki: 79.6 nM (FIH); 2786 nM (PHD2)[1]
ZG-2305 targets factor inhibiting hypoxia-inducible factor (FIH), an asparaginyl hydroxylase that negatively regulates the transcriptional activity of HIF-1alpha and HIF-2alpha. By inhibiting FIH with a Ki of 79.6 nM and showing 38-fold selectivity over the related enzyme PHD2 (Ki 2786 nM), ZG-2305 increases the transcriptional activity of HIF, leading to upregulation of target genes involved in metabolism, including EGLN3. This results in reduced lipid accumulation and improved metabolic profiles. |
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| ln Vitro |
ZG-2305 is a potent FIH inhibitor with a Ki of 79.6 nM. In cellular assays, it increases EGLN3 gene expression and reduces cellular triglyceride levels. It decreases lipid accumulation in hepatocytes, indicating potential benefits in fatty liver disease. The 38-fold selectivity over PHD2 is important to avoid off-target effects on HIF stability. The compound is orally active and has shown efficacy in in vivo models of obesity and NASH.
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| ln Vivo |
ZG-2305 is able to restore abnormal body weight and hepatic steatosis in diet-induced obese male mice and improve HF-CDAA (choline-deficient L-amino acid defined as high-fat) diet-induced NASH in a mouse model of NASH (non- Alcoholic steatohepatitis)-related liver injury, steatosis, inflammation, and fibrosis [1].
ZG-2305 reverses high-fat diet-induced body weight gain and hepatic steatosis in male mice. In an HF-CDAA diet-induced NASH (non-alcoholic steatohepatitis) model, it ameliorates liver injury, steatosis, inflammation, and fibrosis. These in vivo activities demonstrate the therapeutic potential of FIH inhibition for the treatment of obesity and fatty liver disease. The compound is orally active and well-tolerated at effective doses. |
| Enzyme Assay |
The inhibitory activity of ZG-2305 is measured using a cell-free FIH activity assay. Procedure: Recombinant human FIH (10 ng) is incubated with varying concentrations of ZG-2305 (0.1-10000 nM) in assay buffer (50 mM Tris-HCl, pH 7.5, 2 mM DTT, 0.1% Tween-20). The reaction is initiated by adding a HIF-1alpha peptide substrate (50 microM) and 2-oxoglutarate (100 microM). After 30 minutes at 37degC, the reaction is stopped, and the hydroxylated product is quantified by a fluorescence-based or mass spectrometry-based assay. The Ki (79.6 nM) is calculated from the dose-response curve using Lineweaver-Burk analysis.
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| Cell Assay |
The cellular activity can be assessed in hepatocytes. Procedure: Primary mouse hepatocytes or HepG2 cells are seeded in 6-well plates (2x10⁵ cells/well). Cells are treated with varying concentrations of ZG-2305 (0.1-100 uM) in culture medium for 24-48 hours. EGLN3 gene expression is measured by qRT-PCR. Cellular triglyceride levels are quantified using a colorimetric triglyceride assay kit. Lipid accumulation is visualized by Oil Red O staining. A reduction in triglycerides and lipid droplets and an increase in EGLN3 expression indicate efficacy.
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| Animal Protocol |
In vivo efficacy can be evaluated in a mouse model of high-fat diet-induced obesity. Procedure: Male C57BL/6J mice (6 weeks) are fed a high-fat diet (60% kcal from fat) for 12 weeks to induce obesity and hepatic steatosis. Mice are then randomized into groups (n=10). ZG-2305 is formulated in a suitable vehicle (e.g., 0.5% methylcellulose) and administered orally at doses of 10, 30, and 100 mg/kg once daily for 4 weeks. Body weight and food intake are measured weekly. At study endpoint, blood is collected for serum triglyceride and ALT measurement. Liver tissue is harvested for histology (H&E and Oil Red O staining) and triglyceride quantification. Liver fibrosis is assessed in the HF-CDAA NASH model using Sirius Red staining.
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| ADME/Pharmacokinetics |
ZG-2305 is orally active. While specific PK parameters (t½, Cmax, AUC) are not provided, its efficacy in oral dosing studies indicates good oral bioavailability. The compound is soluble in DMSO (125 mg/mL). For in vivo studies, it is typically formulated in 10% DMSO, 40% PEG300, 5% Tween 80, and 45% saline. The powder is stored at -20degC for up to 3 years.
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| Toxicity/Toxicokinetics |
Specific toxicology data for ZG-2305 is not provided. In the HF-CDAA diet-induced NASH model, the compound was well-tolerated at the tested doses, with no reports of significant body weight loss or overt toxicity. However, comprehensive toxicological studies are required. Standard safety precautions for handling research chemicals should be followed.
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| References | |
| Additional Infomation |
ZG-2305 is a selective and orally active FIH inhibitor with 38-fold selectivity over PHD2 (Ki 79.6 nM vs. 2786 nM). It increases EGLN3 gene expression and reduces cellular triglyceride levels. It has shown efficacy in reversing high-fat diet-induced obesity and hepatic steatosis in mice and in ameliorating NASH-related liver injury, steatosis, inflammation, and fibrosis. It is for research use only and is not an approved drug.
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| Molecular Formula |
C17H11CL2N3O5
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|---|---|
| Molecular Weight |
408.19
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| CAS # |
2962103-54-2
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| Appearance |
Typically exists as solids at room temperature
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4498 mL | 12.2492 mL | 24.4984 mL | |
| 5 mM | 0.4900 mL | 2.4498 mL | 4.8997 mL | |
| 10 mM | 0.2450 mL | 1.2249 mL | 2.4498 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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