Home>>Signaling Pathways>> Apoptosis>> Caspase>>Z-VAD-FMK

Z-VAD-FMK

Catalog No.GC12861

Z-VAD-FMK Chemical Structure

Cell-permeable, irreversible pan-caspase inhibitor

Size Price Stock Qty
10mM (in 1mL DMSO)
$103.00
In stock
1mg
$39.00
In stock
5mg
$107.00
In stock
10mg
$192.00
In stock
25mg
$269.00
In stock

Customer Reviews

Based on customer reviews.

Tel: (626) 353-8530 Email: sales@glpbio.com

Sample solution is provided at 25 µL, 10mM.

Quality Control

Quality Control & SDS

View current batch:

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.

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

Chemical Properties

Cas No. 187389-52-2 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
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

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.

  • Molarity Calculator

  • Dilution Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
**When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / CoA (available online).

Calculate

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.
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.