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Purity: ≥98%
Z-VAD-FMK (Z-VAD(OMe)-FMK; Z-Val-Ala-Asp(OMe)-FMK), a peptide compound, is a novel, potent cell-permeable and irreversible (covalent) inhibitor of pan-caspase. It also inhibits ubiquitin carboxy-terminal hydrolase L1 (UCHL1). UCHL1's active site is the target of an irreversible modification by Z-VAD(OMe)-FMK. Instead of stopping CPP32's proteolytic activity directly, Z-VAD-FMK inhibits apoptosis by preventing the activation of proCPP32 into its active state. Large DNA fragments of kilobase pairs that are produced as a result of various stimuli are prevented from forming by Z-VAD-FMK. Z-VAD-FMK had little to no impact on STS-induced necrotic cell death, indicating that the ICE-like protease activity was not involved in necrosis.
| Targets |
Caspase
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|---|---|
| ln Vitro |
Z-VAD-FMK (10 μM) prevents THP.1 cells from going into apoptosis. The PARP protease activity is inhibited by Z-VAD-FMK (10 μM) in control THP. Lysates of 1 cell. In intact THP.1 and Jurkat cells, Z-VAD-FMK (10 μM) prevents CPP32 from being processed. [1] The apoptotic morphology of camptothecin-treated HL60 cells is eliminated by Z-VAD-FMK (50 μM) cotreatment. Camptothecin-induced DNA fragmentation in HL60 cells is blocked by Z-VAD-FMK (50 μM).[2] Z-VAD-FMK (50 μM) prevents cell death in S2 cells after dSMN dsRNA-induced apoptosis. Z-VAD-FMK (50 μM) raises the survival rate of transfected cells in S2 cells from 26% to 63%. [3] Lower concentrations of Z-VAD-FMK (1–30 μM) completely inhibit TNF-stimulated apoptosis in human neutrophils while higher concentrations (>100 μM) enhance TNF-induced neutrophil apoptosis.[4] Inhibiting apoptosis in anterior stromal keratocytes with Z-VAD-FMK (10 mM). When TUNEL assay is used to identify anterior stromal keratocytes, Z-VAD-FMK (10 mM) inhibits apoptosis.[5]
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| ln Vivo |
Z-VAD-FMK administration in vivo has been demonstrated to be nontoxic and to stop apoptosis in animal models in the past. Preterm delivery in mice is delayed by pretreatment with Z-VAD-FMK after intraperitoneal injection of HK-GBS. Treatment with z-VAD-fmk prevents allergen-induced leukocyte infiltration in mice with OVA sensitization. The pan-caspase inhibitor z-VAD-fmk was intravenously injected into mice prior to OVA challenge to reduce inflammatory cell accumulation, mucus hypersecretion, and Th2 cytokine release. Treatment with z-VAD-fmk prevented the terminal differentiation of erythroid progenitors, monocytes into macrophages, and lens epithelial cells as well as keratinocytes. Z-VAD-fmk reduced the inflammation and hyperreactivity of the airways brought on by allergens. Later T cell activation ex vivo was also prevented by z-VAD-fmk treatment in vivo[7].
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| Enzyme Assay |
Interleukin-1 beta converting enzyme (ICE)-like proteases, which are synthesized as inactive precursors, play a key role in the induction of apoptosis. We now demonstrate that benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone (Z-VAD.FMK), an ICE-like protease inhibitor, inhibits apoptosis by preventing the processing of CPP32 to its active form. These results suggest that novel inhibitors of apoptosis can be developed which prevent processing of proforms of ICE-like proteases[1].
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| Cell Assay |
To validate the efficacy of Z-VAD-FMK, three human granulosa cell lines (GC1a, HGL5, COV434) were treated for 48 h with etoposide (50 μg/ml) and/or Z-VAD-FMK (50 μM) under normoxic conditions. Cells were cultured without serum under hypoxia (1% O2) and treated with Z-VAD-FMK in an effort to replicate the ischemic phase that develops after the transplantation of an ovarian fragment. By using the WST-1 assay, the cells' metabolic activity was assessed. Using FACS analyses, cell viability was evaluated. By using RT-qPCR and Western blot analyses, the expression of molecules connected to apoptosis was evaluated.
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| Animal Protocol |
CD1 mice
10 mg/kg i.p. Caspases and apoptosis are thought to play a role in infection-associated preterm-delivery. We have shown that in vitro treatment with pancaspase inhibitor Z-VAD-FMK protects trophoblasts from microbial antigen-induced apoptosis. Objective. To examine whether in vivo administration of Z-VAD-FMK would prevent infection-induced preterm-delivery. Methods. We injected 14.5 day-pregnant-mice with heat-killed group B streptococcus (HK-GBS). Apoptosis within placentas and membranes was assessed by TUNEL staining. Calpain expression and caspase-3 activation were assessed by immunohistochemistry. Preterm-delivery was defined as expulsion of a fetus within 48 hours after injection. Results. Intrauterine (i.u.) or intraperitoneal (i.p.) HK-GBS injection led to preterm-delivery and induced apoptosis in placentas and membranes at 14 hours. The expression of calpain, a caspase-independent inducer of apoptosis, was increased in placenta. Treatment with the specific caspase inhibitor Z-VAD-FMK (i.p.) prior to HK-GBS (i.p.) delayed but did not prevent preterm-delivery. Conclusion. Caspase-dependent apoptosis appears to play a role in the timing but not the occurrence of GBS-induced preterm delivery in the mouse.[7] |
| References | |
| Additional Infomation |
Z-Val-Ala-Asp(OMe)-CH2F is a tripeptide consisting of Z-Val-Ala-Asp(OMe) in which the C-terminal OH group has been replaced by a fluoromethyl group. An irreversible pan-caspase inhibitor. It has a role as an apoptosis inhibitor and a protease inhibitor. It is a carbamate ester, a tripeptide and an organofluorine compound.
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| Molecular Formula |
C22H30FN3O7
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|---|---|
| Molecular Weight |
467.49
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| Exact Mass |
467.206
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| Elemental Analysis |
C, 56.52; H, 6.47; F, 4.06; N, 8.99; O, 23.96
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| CAS # |
187389-52-2
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| Related CAS # |
Z-VAD-FMK;161401-82-7
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| PubChem CID |
5497174
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| Appearance |
White to light yellow solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
732.4±60.0 °C at 760 mmHg
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| Flash Point |
396.7±32.9 °C
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| Vapour Pressure |
0.0±2.4 mmHg at 25°C
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| Index of Refraction |
1.510
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| LogP |
3.4
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
14
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| Heavy Atom Count |
33
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| Complexity |
696
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| Defined Atom Stereocenter Count |
3
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| SMILES |
FC([H])([H])C([C@]([H])(C([H])([H])C(=O)OC([H])([H])[H])N([H])C([C@]([H])(C([H])([H])[H])N([H])C([C@]([H])(C([H])(C([H])([H])[H])C([H])([H])[H])N([H])C(=O)OC([H])([H])C1C([H])=C([H])C([H])=C([H])C=1[H])=O)=O)=O
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| InChi Key |
MIFGOLAMNLSLGH-QOKNQOGYSA-N
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| InChi Code |
InChI=1S/C22H30FN3O7/c1-13(2)19(26-22(31)33-12-15-8-6-5-7-9-15)21(30)24-14(3)20(29)25-16(17(27)11-23)10-18(28)32-4/h5-9,13-14,16,19H,10-12H2,1-4H3,(H,24,30)(H,25,29)(H,26,31)/t14-,16-,19-/m0/s1
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| Chemical Name |
methyl (3S)-5-fluoro-3-[[(2S)-2-[[(2S)-3-methyl-2-(phenylmethoxycarbonylamino)butanoyl]amino]propanoyl]amino]-4-oxopentanoate
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| Synonyms |
Z-VAD-FMK; Z-VAD(OMe)-FMK; Z-Val-Ala-Asp(OMe)-FMK; Z VADFMK; 187389-52-2; Z-VAD(OMe)-FMK; Z-Val-Ala-Asp(OMe)-FMK; pan-caspase inhibitor; C22H30FN3O7; ZVAD-FMK; Z-VAD (OMe)-FMK; ZVADFMK
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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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.62 mg/mL (5.60 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.62 mg/mL (5.60 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. 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: ≥ 2.5 mg/mL (5.35 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. Solubility in Formulation 4: ≥ 2.5 mg/mL (5.35 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 25.0 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. Solubility in Formulation 5: ≥ 2.5 mg/mL (5.35 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 6: ≥ 0.52 mg/mL (1.11 mM) (saturation unknown) in 1% DMSO 99% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 7: 2% DMSO+35 %PEG 300+2%Tween 80+ddH2O: 6mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1391 mL | 10.6954 mL | 21.3908 mL | |
| 5 mM | 0.4278 mL | 2.1391 mL | 4.2782 mL | |
| 10 mM | 0.2139 mL | 1.0695 mL | 2.1391 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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