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Z-VAD-FMK (Synonyms: Benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone,Z-Val-Ala-Asp(OMe)-FMK)

Catalog No.GC12861

Z-VAD-FMK (Z-Val-Ala-Asp(OMe)-FMK) is a cell-permeable and irreversible pan-caspase inhibitor. Z-VAD-FMK is an ubiquitin carboxy-terminal hydrolase L1 (UCHL1) inhibitor. Z-VAD-FMK irreversibly modifies UCHL1 by targeting the active site of UCHL1.

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Z-VAD-FMK Chemical Structure

Cas No.: 187389-52-2

Size Price Stock Qty
10mM (in 1mL DMSO)
$103.00
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1mg
$40.00
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5mg
$109.00
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10mg
$195.00
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25mg
$274.00
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100mg
$850.00
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300mg
$3,914.00
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Sample solution is provided at 25 µL, 10mM.

Product has been cited by 14 publications

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Z-VAD-FMK (Benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone), an ICE-like protease inhibitor, inhibits apoptosis by preventing the processing of CPP32 to its active form. [3]

Z-VAD-FMK is immunosuppressive in vitro and inhibit T cell proliferation without blocking the processing of caspase-8 and caspase-3. Z-VAD-FMK is capable of inhibiting T cell proliferation induced by anti-CD3 plus anti-CD28 or PHA. Besides, z-VAD-FMK inhibits caspase processing during apoptosis but not during T cell activation. Z-VAD-FMK Inhibits caspase processing and apoptosis induction in tumor cells in vitro (IC50 = 0.0015 - 5.8 mM). [1]

Z-VAD-FMK, can be used to induce necroptosis under certain stimuli. Treatment of mice with Z-VAD-FMK could significantly reduce mortality and alleviate disease after lipopolysaccharide (LPS) challenge. Notably, in LPS-challenged mice, treatment with Z-VAD-FMK could also reduce the percentage of peritoneal macrophages by promoting necroptosis and inhibiting pro-inflammatory responses in macrophages. What’s more, pretreatment with Z-VAD-FMK promoted LPS-induced nitric oxide-mediated necroptosis of bone marrow-derived macrophages (BMDMs), leading to reduced pro-inflammatory cytokine secretion. Interestingly, Z-VAD-FMK treatment promoted the accumulation of myeloid-derived suppressor cells (MDSCs) in a mouse model of endotoxin shock, and this process inhibited LPS-induced pro-inflammatory responses in macrophages. Treatment with Z-VAD-FMK alleviates LPS-induced endotoxic shock by inducing macrophage necroptosis and promoting MDSC-mediated inhibition of macrophage activation. For in vivo experienment, the mice were pretreated or post-treated with Z-VAD-FMK (5, 10, and 20 μg/g of body weight) or vehicle (saline) for 2 h and endotoxic shock was induced by an intraperitoneal injection of LPS (10 μg/g of body weight) and saline was used as control. [2]

References:
[1]. Lawrence CP, 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.
[2]. Li X, Yao X, Zhu Y, et al. The Caspase Inhibitor Z-VAD-FMK Alleviates Endotoxic Shock via Inducing Macrophages Necroptosis and Promoting MDSCs-Mediated Inhibition of Macrophages Activation. Front Immunol. 2019 Aug 2;10:1824.
[3]. Slee EA, Zhu H, 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) (Pt 1):21-4.

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