What is Z-VAD-FMK?
Z-VAD-FMK (carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]- fluoromethylketone) is a cell-permeant pan caspase inhibitor that irreversibly binds to the catalytic site of caspase proteases and can inhibit induction of apoptosis.
How does zVAD FMK work?
Z-VAD-FMK inhibits caspases by irreversibly binding to their catalytic site [1]. To conclude, this broad-spectrum inhibitor is a useful tool for studying the role of caspases in inflammation and cell death.
What is pan caspase?
Pan-caspase inhibitors act on one or more of the known caspases and are pursued for their ability to treat diseases such as autoimmune disorders and cancer. Pan-caspase inhibitors can either be peptides, proteins, or small molecule inhibitors.
What is caspase inhibitor?
Caspases are a family of cytosolic aspartate-specific cysteine proteases involved in the initiation and execution of apoptosis. They are expressed as latent zymogens and are activated by an autoproteolytic mechanism or by processing by other proteases (frequently other caspases).
What are SMAC mimetics?
SMAC mimetics are a new class of targeted drugs being developed for the treatment of solid tumours and hematologic cancers. SMAC mimetics specifically induce apoptotic cancer cell death and block pro-survival signalling in cancer cells.
How do you inhibit apoptosis?
Studies have shown that the Bcl-2 oncogene may inhibit apoptosis in two ways; either by directly controlling the activation of caspases, or by disrupting the channels that allow proapoptotic factors from leaving the mitochondria.
Why is caspase so named?
They are named caspases due to their specific cysteine protease activity – a cysteine in its active site nucleophilically attacks and cleaves a target protein only after an aspartic acid residue. Caspases also have a role in inflammation, whereby it directly processes pro-inflammatory cytokines such as pro-IL1β.
What is zVAD?
The compound z-VAD-FMK (zVAD), a pan-caspase inhibitor that prevents apoptosis in many different cell types, can trigger necroptosis by inhibiting the activity of caspase-8, which can be triggered by many inflammatory stimuli including Toll-like receptor 3 and 4 agonists, TNF-α, and certain viral infections (19).
How are caspases activated?
Initiator caspases are activated by intrinsic and extrinsic apoptopic pathways. This leads to the activation of other caspases including executioner caspases that carry out apoptosis by cleaving cellular components.
What are IAP antagonists?
IAP antagonists are a class of compounds that were developed to induce cancer cell death by blocking the caspase inhibitory function of the IAP protein XIAP, but were found to bind with tenfold higher affinity to the cellular IAPs cIAP1 and cIAP2 (ref. 1).
What is SMAC drug?
What can Z-VAD-fmk be used for?
Z-VAD-FMK is used in apoptosis studies and also in inflammasome studies. It is a potent inhibitor of caspase-1 activation in NLRP3-induced cells [2].
Which is the pan caspase inhibitor of Z-VAD-fmk?
Z-VAD-FMK is a cell-permeable pan-caspase inhibitor [1, 2]. It potently inhibits human caspase-1 to -10 with the exception of caspase-2. It also inhibits murine caspases, notably caspase-1, caspase-3, and caspase-11, the ortholog of human caspase-4 and -5 [4, 5].
How long is Z-VAD-fmk stable at room temperature?
Z-VAD-FMK is shipped at room temperature. Upon receipt, store at -20°C. Resuspended product is stable for at least 6 months when properly stored. Avoid repeated freeze-thaw cycles. The caspase enzymes are a family of cytosolic proteases involved in the regulation of inflammation and cell death [1, 2].
How does Z-VAD fmk inhibit NLRP3 inflammasome response?
Z-VAD-FMK inhibits the NLRP3 inflammasome response in a dose-dependent manner. THP1-Null2 cells, primed with LPS‑EK (1 μg/ml for 3 h), were stimulated with MSU crystals (150 µg/ml) and increasing concentrations of Z-VAD‑FMK.