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MCC950 sodium
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
MCC950 sodium图片
CAS NO:256373-96-3
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW) 426.46
Formula C20H23N2O5S.Na
CAS No.256373-96-3 (Sodium salt);
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 85 mg/mL (199.31 mM)
Water: >30 mg/mL
Ethanol: 40 mg/mL (93.79 mM)
SMILES CodeO=S(C1=CC(C(C)(O)C)=CO1)([N-]C(NC2=C3CCCC3=CC4=C2CCC4)=O)=O.[Na+]
Synonyms

CP-45677; CP45677; CP 45677; MCC950; MCC 950; MCC-950; CRID-3; CRID3; CRID 3; CP-456773 sodium

Chemical Name: sodium ((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)((4-(2-hydroxypropan-2-yl)furan-2-yl)sulfonyl)amide

实验参考方法
In Vitro

In vitro activity: MCC950 sodium, the sodium salt of MCC950 (also known as MCC-950, CP-456773 or CRID3), is a potent, selective, small-molecule inhibitor of NLRP3 that has the potential for the treatment of inflammatory diseases and diabetic encephalopathy (DEP). MCC950 blocked canonical and noncanonical NLRP3 activation at nanomolar concentrations. MCC950 specifically inhibited activation of NLRP3 but not the AIM2, NLRC4 or NLRP1 inflammasomes. MCC950 reduced interleukin-1β (IL-1β) production in vivo and attenuated the severity of experimental autoimmune encephalomyelitis (EAE), a disease model of multiple sclerosis. Furthermore, MCC950 treatment rescued neonatal lethality in a mouse model of CAPS and was active in ex vivo samples from individuals with Muckle-Wells syndrome. MCC950 is thus a potential therapeutic for NLRP3-associated syndromes, including autoinflammatory and autoimmune diseases, and a tool for further study of the NLRP3 inflammasome in human health and disease. In addition, inhibiting the NLRP3 Inflammasome sctivation with MCC950 may ameliorate diabetic encephalopathy (DEP) in db/db mice.


Kinase Assay: MCC950 inhibits canonical and noncanonical NLRP3 activation in BMDM and HMDM cells at IC50 of 7.5 and 8.1nM. MCC950 specifically inhibits activation of NLRP3 but not the AIM2, NLRC4 or NLRP1 inflammasomes. 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


Cell Assay: 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.

In VivoMCC950 reduces interleukin-1β (IL-1β) production and attenuates the severity of experimental autoimmune encephalomyelitis (EAE). Furthermore, MCC950 treatment rescues neonatal lethality in a mouse model of CAPS and is active in ex vivo samples from individuals with Muckle-Wells syndrome.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.
Animal model C57BL/6 mice
Formulation & Dosage i.p.
References Nat Med. 2015 Mar;21(3):248-55.