Z-VAD-FMK

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Pan-caspase inhibitor
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 [3]. It also inhibits murine caspases, notably caspase-1, caspase-3, and caspase-11, the ortholog of human caspase-4 and -5 [4, 5]. Caspases are a family of cysteine proteases that are centrally involved in cell death and inflammation responses [6, 7]. 

Mode of action:

Z-VAD-FMK inhibits caspases by irreversibly binding to their catalytic site [1]. By inhibiting the activity of multiple caspases, Z-VAD-FMK can block many different biological processes including inflammasome activation and the induction of apoptosis leading to increased cell survival in many different cell types [2-5]. Interestingly, It has been shown that Z-VAD‑FMK administration can significantly reduce inflammation and lethality in an experimental model of endotoxic shock [5]. To conclude, this broad-spectrum inhibitor is a useful tool for studying the role of caspases in inflammation and cell death.

Key features:

  • Broad-spectrum caspase inhibitor
  • Potent inhibitor of caspase-dependent inflammasomes
  • Blocks the induction of apoptosis
  • Each lot is highly pure (≥95%) and functionally tested 

References:

  1. Slee EA. et al., 1996. Benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone (Z-VAD.FMK) inhibits apoptosis by blocking the processing of CPP32. Biochem J. 315 ( Pt 1):21-4.
  2. Li X. et al., 2019. The caspase inhibitor Z-VAD-FMK alleviates endotoxic shock via inducing macrophages necroptosis and promoting MDSCs-mediated inhibition of macrophages activation. Front Immunol. 10:1824.
  3. Chauvier D. et al., 2007. Broad-spectrum caspase inhibitors: from myth to reality? Cell Death Differ. 14:387-91.
  4. Guey B. et al., 2014. Caspase-1 autoproteolysis is differentially required for NLRP1b and NLRP3 inflammasome function. PNAS 11(48):17254-9.
  5. Py B.F. et al., 2014. Caspase-11 controls interleukin-1β release through degradation of TRPC1. Cell Rep. 6: 1122–8.
  6. Van Opdenbosch N. & Lamkanfi M. et al., 2019. Caspases in Cell Death, Inflammation, and Disease. Immunity. 50(6):1352-1364.
  7. Tsuchiya K. et al., 2019. Caspase-1 initiates apoptosis in the absence of gasdermin D. Nat Commun. 10(1):2091.

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