| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Caspase-2
Z-VDVAD-FMK primarily targets caspase-2, a member of the caspase family involved in apoptosis initiation. It exhibits competitive and irreversible inhibition by binding to the active site cysteine residue. The compound also inhibits caspase-3 and caspase-7, which are crucial enzymes in the execution phase of apoptosis. By inhibiting these caspases, Z-VDVAD-FMK effectively blocks the proteolytic cascade that leads to cell death, making it a valuable tool for studying the molecular mechanisms of apoptosis and for evaluating the role of specific caspases in various pathological conditions. |
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| ln Vitro |
Although many morphological features of apoptosis are prevented when cells are cotreated with the caspase inhibitors Ac-DEVD-CHO, Z-VDVAD-FMK (100 μM), Z-IETD-fmk, and Z-LEHD-fmk alone or in combination, or when CrmA is overexpressed, these effects do not prevent cell death, loss of mitochondrial membrane potential (DCm), or exposure to phospatidilserine[1]. HMEC-1 cells stimulated by Thrombin exhibit significant reduction in Rho-kinase activity when Z-VDVAD-FMK (2 μM) is added; control cells show no change in response to this agent. Reduced avastatin-induced apoptosis is the result of Z-VDVAD-FMK (zVDVAD-fmk). DNA loss caused by lovastatin is considerably decreased by 19.1±8.3% when Z-VDVAD-FMK (100 μM) is used[3].
In vitro studies demonstrate that Z-VDVAD-FMK effectively inhibits apoptosis in various cell lines. The compound reduces lovastatin-induced apoptosis by blocking caspase-2 activity. It is cell-permeable, allowing for direct application to cultured cells. In vitro assays typically measure the compound's ability to inhibit caspase activity using fluorogenic substrates, with the FMK group forming an irreversible covalent bond with the enzyme's catalytic cysteine. The compound's potency is assessed by determining IC₅0 values in enzyme activity assays, with typical concentrations ranging from 0.1-100 microM depending on the cell type and assay conditions. |
| ln Vivo |
In vivo studies demonstrate that Z-VDVAD-FMK has protective effects in animal models of apoptosis-related pathology. Intravitreal injection of Z-VDVAD-FMK (4,000 ng/mL) reduces retinal ganglion cell apoptosis following optic nerve crush injury in rats. It also prevents endothelial cell apoptosis in a dog model of subarachnoid hemorrhage-induced chronic cerebral vasospasm. These findings highlight the therapeutic potential of caspase-2 inhibition in neurodegenerative and vascular diseases. The compound is typically administered via local injection or systemic routes in animal studies, with dosing regimens optimized for specific disease models.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for Z-VDVAD-FMK involve measuring its inhibitory activity against purified caspase enzymes. The assay typically uses recombinant human caspase-2, caspase-3, or caspase-7 and a fluorogenic substrate such as Ac-VDVAD-AFC or Ac-DEVD-AFC. The compound is incubated with the enzyme and substrate at 37degC for 30-60 minutes, and fluorescence is measured to determine enzyme activity. IC₅0 values are calculated from dose-response curves. The irreversible nature of inhibition is confirmed by dialysis or dilution experiments, where activity does not recover after removal of unbound inhibitor.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: The human T-cell leukemia Jurkat (Clone E6.1, ATCC TIB-152) Tested Concentrations: 100 μM Incubation Duration: 22 hrs (hours) Experimental Results: Prevented Doxorubicin (1 μM)-induced nuclear apoptosis, but not cell death. Cellular assays for Z-VDVAD-FMK involve treating cultured cells with the compound to assess its anti-apoptotic effects. Cells are typically pre-treated with Z-VDVAD-FMK (1-100 microM) for 1-2 hours prior to exposure to apoptotic stimuli such as lovastatin, staurosporine, or UV irradiation. Apoptosis is quantified using assays for caspase-3/7 activity, Annexin V/PI staining by flow cytometry, or DNA fragmentation analysis. The compound's ability to inhibit apoptosis is assessed by comparing the percentage of apoptotic cells in treated versus untreated control groups. Cell viability is measured using MTT or similar assays. |
| Animal Protocol |
In vivo animal experiments with Z-VDVAD-FMK are conducted in rodent models of disease where apoptosis plays a significant role. In rat models of optic nerve injury, the compound is administered via intravitreal injection at doses of 4,000 ng/mL to evaluate neuroprotective effects. In dog models of subarachnoid hemorrhage, the compound is used to prevent endothelial cell apoptosis and vasospasm. Dosing regimens, routes of administration, and treatment duration vary depending on the specific model. Endpoints include histological assessment of apoptosis (TUNEL staining), functional outcome measures, and biochemical markers of caspase activity in tissue samples.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Z-VDVAD-FMK are characteristic of peptide-based inhibitors, with limited oral bioavailability due to proteolytic degradation. The compound is cell-permeable, allowing it to reach intracellular targets. It is typically administered via injection (intravitreal, intraperitoneal, or intravenous) in vivo. The compound is soluble in DMSO and stored at -20degC. Its molecular weight is 695.73 g/mol. Due to the irreversible nature of its binding, its pharmacodynamic effects may persist beyond its presence in the circulation. Detailed PK parameters are not extensively reported in the literature.
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| Toxicity/Toxicokinetics |
Toxicological data for Z-VDVAD-FMK are limited, as the compound is used primarily as a research tool rather than a therapeutic agent. The compound is not intended for human therapeutic use and is supplied for research purposes only. In cell-based assays, Z-VDVAD-FMK is generally well-tolerated at concentrations up to 100 microM, though higher concentrations may cause non-specific effects. In animal studies, the compound is typically well-tolerated at standard dosing ranges, with no significant toxicity reported in the literature. Standard safety precautions include handling with appropriate personal protective equipment due to its reactive FMK group.
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| References |
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| Additional Infomation |
Z-VDVAD-FMK is a specific and irreversible inhibitor of caspase-2 that also inhibits caspase-3 and caspase-7. It is a cell-permeable compound that functions as a valuable research tool for studying apoptosis and cell death mechanisms. The compound reduces lovastatin-induced apoptosis and has shown protective effects in animal models of optic nerve injury and subarachnoid hemorrhage. It is supplied as a white powder with ≥95% purity. The compound is not an FDA-approved drug and has no clinical indications. It is typically stored at -20degC and protected from light.
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| Molecular Formula |
C32H46FN5O11
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| Molecular Weight |
695.73
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| Exact Mass |
695.318
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| CAS # |
210344-92-6
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| Related CAS # |
Z-VDVA-(DL-Asp)-FMK;1926163-61-2
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| PubChem CID |
44135215
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| Appearance |
White to off-white solid powder
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| LogP |
3.782
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
22
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| Heavy Atom Count |
49
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| Complexity |
1180
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
ANTIWMNLIROOQF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C32H46FN5O11/c1-17(2)26(30(44)34-19(5)28(42)35-21(23(39)15-33)13-24(40)47-6)37-29(43)22(14-25(41)48-7)36-31(45)27(18(3)4)38-32(46)49-16-20-11-9-8-10-12-20/h8-12,17-19,21-22,26-27H,13-16H2,1-7H3,(H,34,44)(H,35,42)(H,36,45)(H,37,43)(H,38,46)
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| Chemical Name |
methyl 5-fluoro-3-[2-[[2-[[4-methoxy-2-[[3-methyl-2-(phenylmethoxycarbonylamino)butanoyl]amino]-4-oxobutanoyl]amino]-3-methylbutanoyl]amino]propanoylamino]-4-oxopentanoate
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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, 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 : ~250 mg/mL (~359.33 mM)
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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 | 1.4373 mL | 7.1867 mL | 14.3734 mL | |
| 5 mM | 0.2875 mL | 1.4373 mL | 2.8747 mL | |
| 10 mM | 0.1437 mL | 0.7187 mL | 1.4373 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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