Ac-YVAD-cmk

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Caspase-1 inhibitor
Ac-YVAD-cmk

Ac-YVAD-cmk is a potent and irreversible inhibitor of the inflammatory enzyme caspase-1 [1]. Caspase-1, also known as IL-1 converting enzyme (ICE), is a cysteine protease that cleaves the precursors of the pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18, as well as the gasdermin D (GSDMD) pore-forming protein [2].

Mode of action:

Ac‑YVAD‑cmk is a tetrapeptide sequence based on the target sequence of caspase-1 in pro‑IL‑1β (YVHD) [1, 3]. This drug was described as blocking inflammatory cell death in experimental models [4]. Additional reports showed that Ac‑YVAD‑cmk effectively blocks inflammasome activation and that it displays anti-inflammatory, anti-apoptotic, and anti-pyroptotic effects [5, 6]. 

Key features:

  • Potent and irreversible inhibitor of caspase-1
  • Weak inhibitor of caspase-4 and caspase-5 (human paralogs of caspase-1)
  • Each lot is highly pure (≥97%) and functionally tested

References

  1. Garcia-Calvo M. et al., 1998. Inhibition of human caspases by peptide-based and macromolecular inhibitors. J Biol Chem. 273(49):32608-13. 
  2. Man S.M. & Kanneganti T.D., 2016.Converging roles of caspases in inflammasome activation, cell death and innate immunity. Nat. Rev. Immunol. 16(1):7-21.
  3. Talanian, R.V., et al., 1997. Substrate specificities of caspase family proteases. J Biol Chem. 272(15):9677‑82.
  4. Schierle GS. et al., 1999. Caspase inhibition reduces apoptosis and increases survival of nigral transplants. Nat Med. 5(1):97-100.
  5. Van Opdenbosch N. et al., 2014. Activation of the NLRP1b inflammasome independently of ASC-mediated caspase-1 autoproteolysis and speck formation. Nat Commun. 5:3209.
  6. Zhang Y. et al, 2014. Involvement of inflammasome activation in lipopolysaccharide-induced mice depressive-like behaviors. CNS Neurosci Ther. 20(2):119-24.

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