Z-VAD-FMK

Size	Price	Stock
10mM (in 1mL DMSO)	$150.00	In stock
1mg	$55.00	In stock
5mg	$150.00	In stock
10mg	$250.00	In stock
25mg	$400.00	In stock

Product Citations

76.Del Olmo I, López JA, et al. "Arabidopsis DNA polymerase ? recruits components of Polycomb repressor complex to mediate epigenetic gene silencing." Nucleic Acids Res. 2016 Jul 8;44(12):5597-614. PMID:26980282
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79.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
80.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
81.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
82.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
83.Hiller, Bradley E., Angela K. Berger, and Pranav Danthi. "Viral gene expression potentiates reovirus-induced necrosis." Virology 484 (2015): 386-394. PMID:26226583
84.Fiesel, Fabienne C, et al. "(Patho‐) physiological relevance of PINK1‐dependent ubiquitin phosphorylation." EMBO reports (2015): e201540514. PMID:26162776
85.Kang, Seokwon, et al. "Caspase-8 scaffolding function and MLKL regulate NLRP3 inflammasome activation downstream of TLR3." Nature communications 6 (2015). PMID:26104484
86.Antonopoulos, Christina, et al. "Caspase-8 as an Effector and Regulator of NLRP3 Inflammasome Signaling." Journal of Biological Chemistry (2015): jbc-M115. PMID:26100631
87.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
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89.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
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91.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
92.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
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Quality Control

Quality Control & MSDS

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Purity = 98.60%

Related Biological Data

Related Biological Data

Biological Activity

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

Protocol

Kinase experiment [1]:
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]:
Cell lines	Human CD4+ (~ 97%) and CD8+ T (~ 98%) cells
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.
Reaction Conditions	24 h
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]:
Animal models	C57BL mice
Dosage form	1.25 mM, ear provocation
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.
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.
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.

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Chemical Properties

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	≥23.37mg/mL in DMSO	Storage	Store at -20°C
Shipping Condition	Evaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request
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.

Research Update

1. 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. doi: 10.1016/j.taap.2012.09.002. Epub 2012 Sep 12.
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.

2. [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.
Abstract
The effects of Z-VAD-FMK, a caspase inhibitor, on T lymphocytes and the elicitation of murine ACD were investigated.

3. Radiation-induced cytochrome c release and the neuroprotective effects of the pan-caspase inhibitor z-VAD-fmk in the hypoglossal nucleus. Exp Ther Med. 2014 Feb;7(2):383-388. Epub 2013 Nov 20.
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.

4. Cinnamaldehyde-induced apoptosis in human hepatoma PLC/PRF/5 cells involves the mitochondrial death pathway and is sensitive to inhibition by cyclosporin A and z-VAD-fmk. Anticancer Agents Med Chem. 2013 Dec;13(10):1565-74.
Abstract
Z-VAD-FMK is a caspase inhibitor that inhibits mitochondria-related apoptotic effects induced by CIN.

5. Intracochlear perfusion of leupeptin and z-VAD-FMK: influence of antiapoptotic agents on gunshot-induced hearing loss. Eur Arch Otorhinolaryngol. 2011 Jul;268(7):987-93. doi: 10.1007/s00405-011-1487-0. Epub 2011 Jan 19.
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.

Background

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