| Z-VAD-FMKCell-permeable, irreversible pan-caspase inhibitor |
Sample solution is provided at 25 µL, 10mM.
- 1.Shi XJ, Yu B, et al. "Structurally novel steroidal spirooxindole by241 potently inhibits tumor growth mainly through ROS-mediated mechanisms." Sci Rep. 2016 Aug 16;6:31607. PMID:27527552
- 2.Russo HM, Rathkey J, et al. "Active Caspase-1 Induces Plasma Membrane Pores That Precede Pyroptotic Lysis and Are Blocked by Lanthanides." J Immunol. 2016 Aug 15;197(4):1353-67. PMID:27385778
- 3.Kang, Seokwon, et al. "Caspase-8 scaffolding function and MLKL regulate NLRP3 inflammasome activation downstream of TLR3." Nature communications 6 (2015). PMID:26104484
- 4.Abrams, Michael J., et al. "Self-repairing symmetry in jellyfish through mechanically driven reorganization." Proceedings of the National Academy of Sciences (2015): 201502497. PMID:26080418
- 5.Fiesel, Fabienne C., et al. "(Patho‐) physiological relevance of PINK1‐dependent ubiquitin phosphorylation." EMBO reports (2015): e201540514. PMID:26162776
- 6.Rodriguez, D. A., et al. "Characterization of RIPK3-mediated phosphorylation of the activation loop of MLKL during necroptosis." Cell Death & Differentiation (2015). PMID:26024392
- 7.Karmakar, Mausita, et al. "Neutrophil IL-1β Processing Induced by Pneumolysin Is Mediated by the NLRP3/ASC Inflammasome and Caspase-1 Activation and Is Dependent on K+ Efflux." The Journal of Immunology (2015): 1401624. PMID:25609842
- 8.Shah A, Vaidya NK, et al. "HIV-1 gp120 induces type-1 programmed cell death through ER stress employing IRE1α, JNK and AP-1 pathway." Sci Rep. 2016 Jan 7;6:18929. PMID:26740125
- 9.Zhao XM, Chen Z, et al. "Hsp90 modulates the stability of MLKL and is required for TNF-induced necroptosis." Cell Death Dis. 2016 Feb 11;7:e2089. PMID:26866270
- 10. Yalon M, Tuval-Kochen L, et al. "Overcoming Resistance of Cancer Cells to PARP-1 Inhibitors with Three Different Drug Combinations." PLoS One. 2016 May 19;11(5):e0155711. PMID:27196668
- 11.Hsieh Y Y, Chou C J, Lo H L, et al. "Repositioning of a cyclin-dependent kinase inhibitor GW8510 as a ribonucleotide reductase M2 inhibitor to treat human colorectal cancer[J]." Cell Death Discovery, 2016, 2.
- 12.Lu, Kang, et al. "The STAT3 inhibitor WP1066 reverses the resistance of chronic lymphocytic leukemia cells to histone deacetylase inhibitors induced by interleukin-6." Cancer Letters (2015). PMID:25636517
- 13.Rayavarapu R R, Heiden B, Pagani N, et al. "The Role of Multicellular Aggregation in the Survival of ErbB2-Positive Breast Cancer Cells during Extracellular Matrix-Detachment[J]". Journal of Biological Chemistry, 2015: jbc. M114. 612754. PMID:25681438
- 14.Xiong, J., et al. "Dysregulated choline metabolism in T-cell lymphoma: role of choline kinase-α and therapeutic targeting." Blood cancer journal 5.3 (2015): 287. PMID:25768400
- 15.Antonopoulos, Christina, et al. "Caspase-8 as an Effector and Regulator of NLRP3 Inflammasome Signaling." Journal of Biological Chemistry (2015): jbc-M115. PMID:26100631
- 16.Hiller, Bradley E., Angela K. Berger, and Pranav Danthi. "Viral gene expression potentiates reovirus-induced necrosis." Virology 484 (2015): 386-394. PMID:26226583
- 17.Tian, Chongchong, et al. "A novel dual EGFR/HER2 inhibitor KU004 induces cell cycle arrest and apoptosis in HER2-overexpressing cancer cells." Apoptosis 20.12 (2015): 1599-1612. PMID:26437915
- 18.Harris, Katharine G., and Carolyn B. Coyne. "Unc93b Induces Apoptotic Cell Death and Is Cleaved by Host and Enteroviral Proteases." PloS one 10.10 (2015): e0141383. PMID:26509685
- 19.Chan, Zou, et al. "Design, Synthesis and Biological Evaluation of 1‐Benzyl‐1H‐pyrazole Derivatives as Receptor Interacting Protein 1 (RIP1) Kinase Inhibitors." Chemical biology & drug design (2015). PMID:26577270
- 20.Duan, Wenwen, et al. "Protein C‐terminal enzymatic labeling identifies novel caspase cleavages during the apoptosis of multiple myeloma cells induced by kinase inhibition." Proteomics (2015). PMID:26552366
- 21. Boyd-Tressler, Andrea, et al. "Chemotherapeutic Drugs Induce ATP Release via Caspase-gated Pannexin-1 Channels and a Caspase/Pannexin-1-Independent Mechanism." Journal of Biological Chemistry (2014): jbc-M114. PMID:25112874
- 22. El Zaoui, Ikram, Francine Behar-Cohen, and Alicia Torriglia. "Glucocorticoids exert direct toxicity on microvasculature: Analysis of cell death mechanisms." Toxicological Sciences (2014): kfu243. PMID:25447644
Quality Control & MSDS
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| Cell-permeable, irreversible pan-caspase inhibitor. Inhibits caspase processing and apoptosis induction in tumor cells in vitro (IC50 = 0.0015 - 5.8 mM). Active in vivo. | ||||||
| Targets | Caspase | |||||
| IC50 | 0.0015 - 5.8 mM | |||||
| Kinase experiment [1]: | |
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Preventing the processing of CPP32 to its active form |
Z-VAD-FMK inhibits apoptosis by inhibiting the activation of CPP32, which presumably blocked the process by interfering directly with the processing of CPP32. |
| Cell experiment [2]: | |
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Cell lines |
Human CD4+ (~ 97%) and CD8+ T (~ 98%) cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
|
Reacting time |
24 h |
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Applications |
Z-VAD-FMK dose-dependently inhibited T cell proliferation mediated through the co-stimulation with anti-CD3 and anti-CD28. Z-IETD-FMK was less effective at 25 and 50 μM, but inhibited T cell proliferation at the 100 μM concentration. |
| Animal experiment [3]: | |
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Animal models |
C57BL mice |
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Dosage form |
1.25 mM, ear provocation |
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Applications |
The right ear swelling degree, weight differences and thickness between two ears in the 1.25 mML Z-VAD-FMK group were significantly lower than those of the negative control (NC). The levels of INF-γ and IL-2 in the ear skin lesions, the mean intensity of BrdU in T lymphocytes, and the percent of activation markers-positive T lymphocytes were all lower than those of NC. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Slee EA1, Zhu H, Chow SC et al. Benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone (Z-VAD.FMK) inhibits apoptosis by blocking the processing of CPP32. Biochem J. 1996 Apr 1;315 ( Pt 1):21-4. [2]. Lawrence CP1, Chow SC. Suppression of human T cell proliferation by the caspase inhibitors, z-VAD-FMK and z-IETD-FMK is independent of their caspase inhibition properties. Toxicol Appl Pharmacol. 2012 Nov 15;265(1):103-12. [3]. Li YY, Yan CL. Inhibition of elicitation of allergic contact dermatitis by topical use of Z-VAD-FMK, a broad caspase inhibitor: experiment in mice. Zhonghua Yi Xue Za Zhi. 2012 Jul 24;92(28):1992-6. | |
Z-VAD-FMK Dilution Calculator
Z-VAD-FMK Molarity Calculator
| Cas No. | 187389-52-2 | SDF | Download SDF |
| Synonyms | Benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone,Z-Val-Ala-Asp(OMe)-FMK | ||
| Chemical Name | methyl (3S)-5-fluoro-3-[[(2S)-2-[[(2S)-3-methyl-2-(phenylmethoxycarbonylamino)butanoyl]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)OCC1=CC=CC=C1 | ||
| Formula | C22H30FN3O7 | M.Wt | 467.49 |
| Solubility | Soluble in DMSO > 10 mM | Storage | Store at -20°C |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. | ||
| Shipping Condition | Evaluation sample solution : ship with blue ice All other available size: ship with RT , or blue ice upon request |
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Abstract
The caspase inhibitor Z-VAD-FMK exhibits immunosuppressive and anti-proliferative activities in T cell without inhibiting the activity of caspases 8 and 3, where it inhibits NF-KB, the expression of CD25 and FasL-induced apoptosis.
Abstract
The effects of Z-VAD-FMK, a caspase inhibitor, on T lymphocytes and the elicitation of murine ACD were investigated.
Abstract
Intracerebroventricular administration of Z-VAD-FMK, a caspase inhibitor restricted by blood-brain barrier, to post-radiation rats resulted in reduced numbers of TUNEL-positive cells in the hypoglossal nucleus, suppressed expression and activation of caspases 3/8/9 and decrease appearance of cytochrome c in the cytosolic fraction.
Abstract
Z-VAD-FMK is a caspase inhibitor that inhibits mitochondria-related apoptotic effects induced by CIN.
Abstract
Early direct infusion of Z-VAD-FMK, a caspase inhibitor, into cochlear leads to accelerated hearing recovery and reduced hair cell loss in pigs suffering gunshot noise-induced trauma.
Z-VAD-FMK, an inhibitor of ICE-like proteases, inhibits apoptosis in THP.1 cells induced by diverse stimuli1 and Fas antigen-induced apoptosis in Jurkat T-cells2. It inhibits apoptosis by blocking the activation of proCPP32 into its active form, rather than by preventing the proteolytic action of CPP32 directly.
Z- VAD-FMK inhibits the formation of large kilobasepair fragments of DNA induced by diverse stimuli. Z-VAD-FMK had little or no effect on STS-induced necrotic cell death suggesting that the ICE-like protease activity was not involved in necrosis3.
Z-VAD-FMK almost completely inhibited the formation of large kilobasepair induced by all four stimuli. Similarly Z-VAD-FMK almost completely inhibited the enhanced formation of large kilobasepair fragments induced by thapsigargin or cycloheximide in the presence of TLCK, in good agreement with its ability to inhibit apoptosis induced by these treatments. These stimuli also induced internucleosomal cleavage of DNA, which was inhibited by Z-VAD-FMK. These results suggested that an ICE-like protease(s) acts at a stage prior to the formation of large kilobasepair fragments of DNA3.
References:
1. Darmon, A.J., Ehrman, N., Caputo, A., Fujinaga, J. and Bleackley, R.C. (1994) J. Biol. Chem. 269, 32043-32046.
2. Chow, S. C., Weis M., Kass, G. E. N., Holmstrom, T. H., Eriksson, J. E. and Orrenius S. (1995) FEBS Lett. 364, 134±138
3. H. Zhu et al./FEBS Letters 374 (1995) 303-308
