Caspase-1 inhibitor - Ac-YVAD-cmk
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Ac-YVAD-cmk is a potent and irreversible inhibitor of the inflammatory caspase-1 . Caspase-1, also known as IL-1 converting enzyme (ICE), is a cysteine protease that cleaves the precursors of the IL-1β and IL-18 pro-inflammatory cytokines, as well as the gasdermin D (GSDMD) pore-forming protein .
CASPASE-1 IN INFLAMMASOME RESPONSES:
Rapid responses to infections and tissue damages are largely mediated by the inflammasomes. The formation of these cytosolic signaling platforms occurs according to a consensual two-step model. The priming step (step 1) induces the transcription of pro-IL-1β. The activation step (step 2) triggers the multimerization of the activated inflammasome sensor with the ASC adaptor and pro-caspase-1. This assembly permits caspase-1 self-activation, which in turn induces the maturation of IL-1β and IL-18 cytokines. Activated caspase-1 also cleaves the N-terminal fragment of GSDMD, which accumulates to form pores at the cell membrane. These pores allow the unconventional secretion of IL-1β and IL-18, and in the absence of membrane repair, their accumulation leads to pyroptosis.
MODE OF ACTION OF Ac-YVAD-cmk:
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 . 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 OF Ac‑YVAD‑cmk:
- 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
Read our review on inflammasomes.
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 SM & Kanneganti TD., 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.
Ac-YVAD-cmk inhibits NLRP3 inflammasome response in a dose-dependent manner.
THP1-Null2 cells were primed with LPS-EK (1 μg/ml) for 3h and then stimulated with MSU crystals (150 µg/ml) and increasing concentrations of Ac‑YVAD‑cmk. After 24h activation, the secretion of mature IL-1β in the culture supernatant was assessed using HEK-Blue™ IL-1β sensor cells and QUANTI‑Blue™ Solution detection reagent. The optical density (OD) was read at 655 nm.
CAS number: 178603-78-6
Synonym: Acetyl-tyrosine-valine-alanine-aspartate‑chloromethyl ketone
Working concentration: 0.1–30 μg/ml for cell culture assays
Solubility: 50 mg/ml (92.4 mM) in DMSO
Molecular weight: 541 g/mol
- Purity: ≥97% (UHPLC)
- The inhibitory activity of the product has been validated in inflammasome cellular assays using THP1-Null2 and HEK-Blue™ IL-1β cells.
- The absence of bacterial contamination (e.g. lipoproteins and endotoxins) has been confirmed using HEK-Blue™ TLR2 and HEK-Blue™ TLR4 cells.
- 5 mg Ac-YVAD-cmk (provided as a powder)
Ac-YVAD-cmk 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.Back to the top
Chemical structure of Ac-YVAD-cmk:
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