1. Immunology/Inflammation
  2. NOD-like Receptor (NLR)

MCC950 sodium (Synonyms: CP-456773 sodium; CRID3 sodium salt)

Cat. No.: HY-12815A Purity: 99.40%
Handling Instructions

MCC950 sodium is a potent, selective NLRP3 inhibitor with IC50 of 7.5 nM and 8.1 nM in BMDMs and HMDMs, respectively.

For research use only. We do not sell to patients.
MCC950 sodium Chemical Structure

MCC950 sodium Chemical Structure

CAS No. : 256373-96-3

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Customer Review

Other Forms of MCC950 sodium:

    MCC950 sodium purchased from MCE. Usage Cited in: J Am Heart Assoc. 2017 Sep 4;6(9). pii: e006347.

    Cells are pretreated with YVAD(10 μM) or MCC950 (10 μM) for 2 hours, and then exposed to TMAO (600 μM) for a further 24 hours. Expression of IL-1β, ICAM-1, MMP-9, and caspase-1 p20 is detected via Western blot.

    MCC950 sodium purchased from MCE. Usage Cited in: Dig Dis Sci. 2017 Oct 23.

    The expression of various molecules in pyroptotic and apoptotic pathways is detected by western blot. Representative bands from densitometric analysis in experimental groups are presented. M, MCC950 group (an inhibitor of NLRP3).

    MCC950 sodium purchased from MCE. Usage Cited in: Biofactors. 2017 Nov 29.

    NLRP3, Casp1 p20, IL-1b, and ICAM-1 protein levels are assessed in the cell lysates by Western blotting.

    MCC950 sodium purchased from MCE. Usage Cited in: Biochim Biophys Acta. 2017 Oct 3;1864(1):1-10.

    MCC950 or vehicle control (PBS) is administered at 1, 4 and 6 day after Ang II infusion in the absence or presence of EMD638683. Representative images and quantification of picrosirius red-stained collagen in the heart at 7 days after Ang II infusion.

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    • Biological Activity

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    • Technical Information

    • Purity & Documentation

    • References

    Description

    MCC950 sodium is a potent, selective NLRP3 inhibitor with IC50 of 7.5 nM and 8.1 nM in BMDMs and HMDMs, respectively.

    IC50 & Target

    IC50: 7.5 nM (NLRP3, in BMDMs), 8.1 nM (NLRP3, in HMDMs)[1]

    In Vitro

    MCC950 blocks canonical and non-canonical NLRP3 activation at nanomolar concentrations. MCC950 specifically inhibits NLRP3 but not AIM2, NLRC4 or NLRP1 activation. The effect of MCC950 on NLRP3 inflammasome activation is tested in mouse bone marrow derived macrophages (BMDM) and human monocyte derived macrophages (HMDM). The IC50 of MCC950 in BMDM is approximately 7.5 nM, while in HMDM it has a similar inhibitory capacity (IC50=8.1 nM). MCC950 also dose dependently inhibit IL-1β but not TNF-α secretion.MCC950 specifically blocks caspase-11-directed NLRP3 activation and IL-1β secretion upon stimulation of the non-canonical pathway. NLRC4-stimulated IL-1β and TNF-α secretion (as activated by Salmonella typhimurium) are not inhibited by MCC950 even at a concentration of 10 µM. MCC950 does not inhibit caspase-1 activation or IL-1β processing in response to S. typhimurium. The expression of pro-caspase-1 and pro-IL-1β in cell lysates is not substantially affected by MCC950 treatment[1].

    In Vivo

    MCC950 reduces Interleukin-1p (IL-1β) production and attenuates the severity of experimental autoimmune encephalomyelitis (EAE), a disease model of multiple sclerosis. Pre-treatment with MCC950 reduces serum concentrations of IL-1β and IL-6 while it does not considerably decrease the amount of TNF-α. Treatment of mice with MCC950 delays the onset and reduced the severity of EAE. Intracellular cytokine staining and FACS analysis of brain mononuclear cells from mice sacrificed on day 22 shows modestly reduced frequencies of IL-17 and IFN-γ producing CD3+ T cells in MCC950 treated mice in comparison with PBS-treated mice. IFN-γ and particularly IL-17 producing cell numbers are also reduced in both the CD4+ and γδ+ sub-populations of CD3+ T cells[1].

    References
    Cell Assay
    [1]

    MCC950 is dissolved in DMSO and stored, and then diluted with appropriate media before use[1].

    BMDM are seeded at 5×105/mL or 1×106/mL, HMDM at 5×105/mL and PBMC at 2×106/mL or 5×106/mL in 96 well plates. The following day the overnight medium is replaced and cells are stimulated with 10 ng/mL LPS from Escherichia coli serotype EH100 (ra) TLRgrad for 3 h. Medium is removed and replaced with serum free medium (SFM) containing DMSO (1:1,000), MCC950 (0.001-10 µM), glyburide (200 µM), Parthenolide (10 µM) or Bayer cysteinyl leukotriene receptor antagonist 1-(5-carboxy-2{3-[4-(3-cyclohexylpropoxy)phenyl]propoxy}benzoyl)piperidine-4-carboxylic acid (40 µM) for 30 min. Cells are then stimulated with inflammasome activators: 5 mM adenosine 5’-triphosphate disodium salt hydrate (ATP) (1 h), 1 µg/mL Poly(deoxyadenylic-thymidylic) acid sodium salt (Poly dA:dT) transfected with Lipofectamine 200 (3-4 h), 200 µg/mL MSU (overnight) and 10 µM nigericin (1 h) or S. typhimurium UK-1 strain. Cells are also stimulated with 25 µg/mL Polyadenylic-polyuridylic acid (4 h). For non-canonical inflammasome activation cells are primed with 100 ng/mL Pam3CSK4 for 4 h, medium is removed and replaced with SFM containing DMSO or MCC950 and 2 µg/mL LPS is transfected using 0.25% FuGENE for 16 h. Supernatants are removed and analysed using ELISA kits. LDH release is measured using the CytoTox96 non-radioactive cytotoxicity assay[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [1]

    MCC950 is dissolved in DMSO and diluted with PBS before use (Mice)[1].

    Mice[1]
    C57BL/6 mice are immunized subcutaneously with 150 µg of MOG peptide 35-55 emulsified in CFA containing 4 mg/mL (0.4.mg/mouse) of heat-killed MTB. Mice are injected i.p. with 500 ng pertussis toxin (PT: kaketsuken) on days 0 and 2. MCC950 is administered i.p. to mice (10 mg/kg) at induction of the disease, day 0, 1 and 2 and every 2 days thereafter. Control mice are administered vehicle (PBS) at the same time points. Mice are observed for clinical signs of disease daily (unblinded). Disease severity is scored as follows: no clinical signs, 0; limp tail, 1; ataxic gait, 2; hind limb weakness, 3; hind limb paralysis, 4; and tetra paralysis, 5. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    426.46

    Formula

    C₂₀H₂₃N₂NaO₅S

    CAS No.

    256373-96-3

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Solvent & Solubility

    H2O: ≥ 30 mg/mL

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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    Product Name:
    MCC950 sodium
    Cat. No.:
    HY-12815A
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