| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Apoptotic protease activating factor-1[1]
Apoptotic protease activating factor-1 (Apaf-1). ZYZ-488 acts as a competitive inhibitor by directly binding to Apaf-1. This binding blocks the recruitment of procaspase-9 to the Apaf-1 apoptosome, thereby preventing the downstream activation of the caspase cascade and inhibiting the intrinsic (mitochondrial) pathway of apoptosis. |
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| ln Vitro |
In hypoxic H9c2 cells, ZYZ-488 reduces apoptosis. ZYZ-488 suppresses procaspase-9 and procaspase-3 activation mediated by Apaf-1 in response to hypoxia[1]. ZYZ-488 suppresses the activation of the downstream caspases cascade, prevents cardiomyocyte death, and reduces the release of cardiac enzymes[2].
ZYZ-488 demonstrates significant in vitro activity by reducing apoptosis in hypoxic H9c2 cardiomyocytes. It inhibits the hypoxia-induced, Apaf-1-mediated activation of procaspase-9 and procaspase-3. In cellular assays, ZYZ-488 enhances cell viability and reduces the leakage of lactate dehydrogenase (LDH) and creatine kinase (CK), which are markers of cell membrane integrity and myocardial injury, respectively. |
| ln Vivo |
ZYZ-488 (intramuscular; 33.9–67.8 mg/kg; 3 days) prevented myocardial apoptosis[2].
In vivo studies in mouse models demonstrate that intramuscular injection of ZYZ-488 (at doses of 33.9 mg/kg or 67.8 mg/kg for 3 days) protects against myocardial apoptosis. Treatment with ZYZ-488 reduces myocardial infarction (MI)-induced increase in left ventricular volume and decreases ventricular wall thickness. The compound preserves cardiac function in a dose-dependent manner. |
| Enzyme Assay |
Surface plasmon resonance (SPR) assays are used to confirm the direct binding between ZYZ-488 and Apaf-1. Kinetic parameters for this binding are determined by injecting varying concentrations of ZYZ-488 over immobilized Apaf-1 and measuring the response in resonance units (RU). These assays help characterize the competitive inhibition mechanism.
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| Cell Assay |
In vitro cellular activity is assessed using hypoxic H9c2 cells. Cells are treated with varying concentrations of ZYZ-488, and apoptosis is evaluated by measuring cell viability, caspase-9 activation, and morphological changes such as chromatin condensation and nuclear fragmentation via Hoechst staining. The leakage of LDH and CK is also measured as indicators of cell damage.
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| Animal Protocol |
Animal/Disease Models: Male C57BL/6 mice (8-10 weeks old)[2]
Doses: myocardial infarction + ZYZ-488 (33.9 mg/kg); myocardial infraction + ZYZ-488 (67.8 mg/kg); Route of Administration: Intramuscularly; for 3 days Experimental Results: Inhibited Apaf- 1-mediated activation of procaspase-9 and procaspase-3. In vivo efficacy is evaluated in mouse models of myocardial ischemia. ZYZ-488 is administered via intramuscular injection at doses of 33.9 mg/kg or 67.8 mg/kg for 3 days. Cardiac function is assessed by measuring left ventricular volume and wall thickness, and myocardial apoptosis is evaluated by analyzing biomarkers like Apaf-1 and caspase-9. |
| ADME/Pharmacokinetics |
ZYZ-488 has a molecular weight of 487.46 and a molecular formula of C20H2₉N3O11. It is soluble in DMSO (200 mg/mL) and water (80 mg/mL). A typical in vivo formulation uses 10% DMSO, 40% PEG300, 5% Tween 80, and 45% saline. The compound should be stored as a powder at -20degC in a dry, dark place.
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| Toxicity/Toxicokinetics |
No specific toxicity data is available in the provided literature. However, as with all research compounds, it is not intended for human use. The compound is classified as non-hazardous for shipping. In vivo studies show that ZYZ-488 is administered at doses that are effective for cardioprotection without overt signs of acute toxicity in mouse models.
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| References | |
| Additional Infomation |
ZYZ-488 is a competitive inhibitor of Apaf-1, a key protein in the intrinsic apoptosis pathway. Its primary mechanism is to prevent the formation of the apoptosome by blocking procaspase-9 recruitment. This compound shows promise in treating cardiac ischemia. It has not entered clinical trials and is exclusively a research tool for studying apoptosis and cardiovascular diseases.
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| Molecular Formula |
C20H29N3O11
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|---|---|
| Molecular Weight |
487.4578
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| Exact Mass |
487.18
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| CAS # |
1470302-79-4
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| PubChem CID |
138454738
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| Appearance |
White to off-white solid powder
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| LogP |
-1
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
34
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| Complexity |
691
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| Defined Atom Stereocenter Count |
5
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| SMILES |
O1[C@]([H])([C@@]([H])([C@]([H])([C@@]([H])([C@@]1([H])C(=O)O[H])O[H])O[H])O[H])OC1C(=C([H])C(C(=O)OC([H])([H])C([H])([H])C([H])([H])C([H])([H])/N=C(\N([H])[H])/N([H])[H])=C([H])C=1OC([H])([H])[H])OC([H])([H])[H]
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| InChi Key |
PVTAIJDQJJZCJP-WXZWTWHISA-N
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| InChi Code |
InChI=1S/C20H29N3O11/c1-30-10-7-9(18(29)32-6-4-3-5-23-20(21)22)8-11(31-2)15(10)33-19-14(26)12(24)13(25)16(34-19)17(27)28/h7-8,12-14,16,19,24-26H,3-6H2,1-2H3,(H,27,28)(H4,21,22,23)/t12-,13-,14+,16-,19+/m0/s1
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| Chemical Name |
(2S,3S,4S,5R,6S)-6-[4-[4-(diaminomethylideneamino)butoxycarbonyl]-2,6-dimethoxyphenoxy]-3,4,5-trihydroxyoxane-2-carboxylic acid
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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) |
DMSO : 200 mg/mL (410.29 mM)
H2O : ≥ 100 mg/mL (205.15 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (10.26 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5 mg/mL (10.26 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 5 mg/mL (10.26 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0515 mL | 10.2573 mL | 20.5145 mL | |
| 5 mM | 0.4103 mL | 2.0515 mL | 4.1029 mL | |
| 10 mM | 0.2051 mL | 1.0257 mL | 2.0515 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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