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| 5mg |
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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
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.
| ln Vitro |
At nanomolar doses, MCC950 prevents both conventional and non-canonical NLRP3 activation. AIM2, NLRC4, and NLRP1 activation are not specifically inhibited by MCC950, whereas NLRP3 is. Using mouse bone marrow-derived macrophages (BMDM) and human monocyte-derived macrophages (HMDM), the impact of MCC950 on NLRP3 inflammasome activation was investigated. MCC950 exhibits an inhibitory capacity of around 7.5 nM in BMDM and 8.1 nM in HMDM. Moreover, MCC950 reduces IL-1β secretion in a dose-dependent manner but not TNF-α secretion. MCC950 stimulates the non-canonical pathway first, then selectively inhibits caspase-11-mediated NLRP3 activation and IL-1β release. MCC950 failed to suppress Salmonella Typhimurium-induced NLRC4-stimulated IL-1β and TNF-α production, even at a dosage of 10 µM. MCC950 had no effect on the processing of IL-1β or caspase-1 activation in response to Salmonella typhimurium. Pro-caspase-1 and pro-IL-1β production in cell lysates is not considerably impacted by MCC950 treatment [1].
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| ln Vivo |
MCC950 attenuates the severity of experimental autoimmune encephalomyelitis (EAE), a disease model of multiple sclerosis, and decreases the production of interleukin-1p (IL-1β). Pretreatment with MCC950 lowers serum concentrations of IL-1β and IL-6 but does not significantly lower TNF-α levels. MCC950 treatment lessens the severity and postpones the development of EAE in mice. When comparing MCC950-treated animals to PBS-treated mice, intracellular cytokine labeling and FACS analysis of brain mononuclear cells from mice killed on day 22 reveal slightly lower frequencies of CD3+ T cells that produce IL-17 and IFN-γ. There is a decrease in the quantity of CD4+ and γδ+ sub-populations of CD3+ T cells that produce IFN-γ, and in particular, IL-17 generating cells[1].
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| References |
[1]. Coll RC, et al. A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nat Med. 2015 Mar;21(3):248-55
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| Molecular Formula |
C20H24N2O5S
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| Molecular Weight |
404.48
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| CAS # |
210826-40-7
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| Related CAS # |
MCC950 sodium;256373-96-3
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| SMILES |
O=S(C1=CC(C(C)(O)C)=CO1)([N-]C(NC2=C3CCCC3=CC4=C2CCC4)=O)=O
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| Synonyms |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.18 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.18 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.18 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4723 mL | 12.3616 mL | 24.7231 mL | |
| 5 mM | 0.4945 mL | 2.4723 mL | 4.9446 mL | |
| 10 mM | 0.2472 mL | 1.2362 mL | 2.4723 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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