Caspase-1 inhibitor - Ac-YVAD-cmkAc-YVAD-cmkUnit sizeCat. codeDocsPriceCaspase-1 inhibitor5 mg inh-yvadTDSMSDSDATA ￥3,637.00Please contact our distributorAdd to favoriteAboutSpecificationsContentsDetailsCitationsRelated products*/Caspase-1 inhibitorInhibition of caspase signaling by Ac-YVAD-cmkAc-YVAD-cmk is a potent and irreversible inhibitor of the inflammatory caspase-1 [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 [2].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 [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 OF Ac‑YVAD‑cmk:Potent and irreversible inhibitor of caspase-1Weak inhibitor of caspase-4 and caspase-5 (human paralogs of caspase-1)Each lot is highly pure (≥97%) and functionally tested Read our review oninflammasomes.  References1. 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.Figures 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. Back to the topSpecificationsCAS number: 178603-78-6Synonym: Acetyl-tyrosine-valine-alanine-aspartate‑chloromethyl ketoneWorking concentration: 0.1–30 μg/ml for cell culture assaysSolubility: 50 mg/ml (92.4 mM) in DMSOFormula: C24H33ClN4O8Molecular weight: 541 g/molQuality control: 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.Back to the topContents5 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 topDetailsChemical structure of Ac-YVAD-cmk: Back to the topCitations2020J Am Coll Cardiol Basic Trans Science. DOI: 10.1016/j.jacbts.2019.10.011Macrophage-Derived Exosomal Mir-155 Regulating Cardiomyocyte Pyroptosis and Hypertrophy in Uremic Cardiomyopathy.Wang B. et al.2019 Am J Pathol. DOI: 10.1016/j.ajpath.2019.06.013Double-Stranded RNA Is a Novel Molecular Target in Osteomyelitis Pathogenesis: A Translational Avian Model for Human Bacterial Chondronecrosis with Osteomyelitis.Greene E. et al.2018 Nat Commun.9(1):863. FcαRI co-stimulation converts human intestinal CD103+ dendritic cells into pro-inflammatory cells through glycolytic reprogramming.Hansen IS. et al.2018 Nat Commun. 9(1):4260.The fungal peptide toxin Candidalysin activates the NLRP3 inflammasome and causes cytolysis in mononuclear phagocytes.Kasper L. et al.2018 Vaccine. DOI: 10.1016/j.vaccine.2018.05.066Combination therapy of rabies-infected mice with inhibitors of pro-inflammatory host response, antiviral compounds and human rabies immunoglobulin.Marosi A. et al.2017 Immunology. 151(4):385-394.Interleukin-18 activates Vγ9Vδ2+ T cells from HIV-positive individuals: recovering the response to phosphoantigen.Murday AS. et al.2017 J Immunol. 199(7):2460-2474.A Plant-Derived Nucleic Acid Reconciles Type I IFN and a Pyroptotic-like Event in Immunity against Respiratory Viruses.Kasumba DM. et al.2017 Cell Prolif. 50(6).IFI16 restoration in hepatocellular carcinoma induces tumour inhibition via activation of p53 signals and inflammasome.Lin W. et al.2016 PLoS One. 11(7):e0160248.Modulation of Pathways Underlying Distinct Cell Death Mechanisms in Two Human Lung Cancer Cell Lines in Response to SN1 Methylating Agents Treatment.Papadodima O. et al.Load moreYou may also needAlumNLRP3 Inflammasome Inducer; Aluminium hydroxideMSU CrystalsNLRP3 Inflammasome Inducer - Monosodium Urate CrystalsNigericinNLRP3 Inflammasome Inducer - Nigericin, sodium saltPoly(dA:dT)RIG-I Agonist - CDS Agonist - AIM2 Inflammasome InducerLPS-EK (LPS from E. coli K12)TLR4 Agonist - Lipopolysaccharide from E. coli K12THP1-Null2 CellsHuman THP-1 Monocytes - Positive Control for Inflammasome StudiesTHP1-HMGB1-Lucia™ CellsPyroptosis and necroptosis reporter monocytesHEK-Blue™ IL-1β CellsHuman & Mouse IL-1β Reporter CellsZ-VAD-FMKPan-caspase inhibitor VX-765Caspase-1 and Caspase-4 inhibitor