Z-VDVAD-FMK (Synonyms: Z-VDVAD-fluoromethylketone, Caspase-2 Inhibitor (fluoromethylketone),Z-Val-Asp(OMe)-Val-Ala-Asp(OMe)-FMK) |
Catalog No.GC11218
One-Click Copy Product Info
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Z-VDVAD-FMK is an irreversible, cell-permeable caspase-2-specific inhibitor.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 210344-92-6
Sample solution is provided at 25 µL, 10mM.
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Z-VDVAD-FMK is an irreversible, cell-permeable caspase-2-specific inhibitor[1-2]. By specifically binding to the active site of caspase-2, Z-VDVAD-FMK effectively blocks caspase-2 signaling pathway, thereby inhibiting the activation of downstream caspases (such as caspase-3) and suppressing apoptosis[3-4].
In vitro, BxPC-3 human pancreatic carcinoma cells were pretreated with Z-VDVAD-FMK (50μM) for 3 hours, followed by treatment with PS-341 (Bortezomib; 100nM) for 24 hours. Z-VDVAD-FMK significantly inhibited PS-341-induced mitochondrial depolarization and apoptosis, and blocked the changes in mitochondrial permeability downstream of caspase-2 activation[5]. HL-60 acute myeloid leukemia cells were pretreated with Z-VDVAD-FMK (10μM) for 2 hours, followed by treatment with Gemtuzumab ozogamicin (GO; 1000ng/mL) for 48 hours. Z-VDVAD-FMK significantly inhibited GO-induced caspase-3 activation and reduced apoptotic signaling. Under GO treatment, Z-VDVAD-FMK also partially inhibited Bid cleavage[6].
In vivo, Z-VDVAD-FMK (400–5000ng/mL; 5μL) was administered via intravitreal injection (on days 0, 4, 8, and 12) in an optic nerve crush (ONC) injury Sprague-Dawley rats model. Z-VDVAD-FMK significantly inhibited ONC-induced caspase-2 activation and reduced the level of apoptosis in retinal ganglion cells[7].
References:
[1] Gamen S, Anel A, Pérez-Galán P, et al. Doxorubicin treatment activates a Z-VAD-sensitive caspase, which causes deltapsim loss, caspase-9 activity, and apoptosis in Jurkat cells. Exp Cell Res. 2000 Jul 10;258(1):223-35.
[2] Sapet C, Simoncini S, Loriod B, et al. I Thrombin-induced endothelial microparticle generation: identification of a novel pathway involving ROCK-II activation by caspase-2. Blood. 2006 Sep 15;108(6):1868-76.
[3] Rabkin SW, Kong JY. Lovastatin-induced cardiac toxicity involves both oncotic and apoptotic cell death with the apoptotic component blunted by both caspase-2 and caspase-3 inhibitors. Toxicol Appl Pharmacol. 2003 Dec 15;193(3):346-55.
[4] Kim BM, Hong SH. Sequential caspase-2 and caspase-8 activation is essential for saikosaponin a-induced apoptosis of human colon carcinoma cell lines. Apoptosis. 2011 Feb;16(2):184-97.
[5] Yeung BH, Huang DC, Sinicrope FA. PS-341 (bortezomib) induces lysosomal cathepsin B release and a caspase-2-dependent mitochondrial permeabilization and apoptosis in human pancreatic cancer cells. J Biol Chem. 2006 Apr 28;281(17):11923-32.
[6] Hååg P, Olsson M, Forsberg J, et al. Caspase-2 is a mediator of apoptotic signaling in response to gemtuzumab ozogamicin in acute myeloid leukemia. Cell Death Discov. 2022 Jun 11;8(1):284.
[7] Vigneswara V, Berry M, Logan A, et al. Pharmacological inhibition of caspase-2 protects axotomised retinal ganglion cells from apoptosis in adult rats. PLoS One. 2012;7(12):e53473.
| Cell experiment [1]: | |
Cell lines | BxPC-3 and CFPAC-1 cells (human pancreatic carcinoma cell lines) |
Preparation Method | BxPC-3 cells were maintained in RPMI 1640 medium supplemented with 10% fetal bovine serum (FBS) at 37°C, 5% CO₂. Cells were preincubated with the caspase-2 inhibitor Z-VDVAD-FMK (50µM) for 3 hours, followed by treatment with the proteasome inhibitor PS-341 (Bortezomib; 100nM) for 24 hours. |
Reaction Conditions | 50µM; 3h preincubation |
Applications | Z-VDVAD-FMK significantly attenuated PS-341-induced mitochondrial depolarization and apoptosis. Z-VDVAD-FMK also suppressed PS-341-induced cytochrome c release but did not affect PS-341-induced reactive oxygen species (ROS) generation or lysosomal cathepsin B redistribution. |
| Animal experiment [2]: | |
Animal models | Adult female Sprague-Dawley rats |
Preparation Method | Rats underwent bilateral optic nerve crush (ONC) 2 mm from the eye. The caspase-2 inhibitor Z-VDVAD-FMK was dissolved in sterile DMSO and diluted in PBS for intravitreal injection. Animals received intravitreal injections of Z-VDVAD-FMK (400-5000ng/ml in 5µl volume) immediately after ONC (day 0), with repeated injections at 4, 8, and 12 days post-ONC. Animals were sacrificed 15 days after ONC for retinal analysis. |
Dosage form | 4000ng/ml in 5µl volume (optimal dose); Intravitreal injection; Administered on days 0, 4, 8, and 12. |
Applications | Z-VDVAD-FMK treatment significantly suppressed cleaved caspase-2 in retinal ganglion cells (RGCs) and protected of RGCs from apoptosis 15 days after ONC compared to vehicle-treated controls. |
References: | |
| Cas No. | 210344-92-6 | SDF | |
| Synonyms | Z-VDVAD-fluoromethylketone, Caspase-2 Inhibitor (fluoromethylketone),Z-Val-Asp(OMe)-Val-Ala-Asp(OMe)-FMK | ||
| Chemical Name | methyl (3S)-5-fluoro-3-[[(2S)-2-[[(2S)-2-[[(2S)-4-methoxy-2-[[(2S)-3-methyl-2-(phenylmethoxycarbonylamino)butanoyl]amino]-4-oxobutanoyl]amino]-3-methylbutanoyl]amino]propanoyl]amino]-4-oxopentanoate | ||
| Canonical SMILES | CC(C)C(C(=O)NC(C)C(=O)NC(CC(=O)OC)C(=O)CF)NC(=O)C(CC(=O)OC)NC(=O)C(C(C)C)NC(=O)OCC1=CC=CC=C1 | ||
| Formula | C32H46N5O11F | M.Wt | 695.73 |
| Solubility | ≥ 34.8mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.4373 mL | 7.1867 mL | 14.3734 mL |
| 5 mM | 287.5 μL | 1.4373 mL | 2.8747 mL |
| 10 mM | 143.7 μL | 718.7 μL | 1.4373 mL |
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Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
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Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)