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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: =98.61%
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.
| ln Vitro |
At nanomolar doses, MCC950 inhibits both conventional and non-canonical NLRP3 activation. MCC950 selectively prevents NLRP3 activation, but not that of AIM2, NLRC4, or NLRP1. Using human monocyte-derived macrophages (HMDM) and mouse bone marrow-derived macrophages (BMDM), the impact of MCC950 on NLRP3 inflammasome activation was investigated. MCC950 exhibits an inhibitory capacity of 8.1 nM in HMDM, compared to its about 7.5 nM IC50 in BMDM. Moreover, MCC950 dose-dependently reduced IL-1β secretion but not TNF-α secretion. MCC950 selectively inhibits NLRP3 activation and IL-1β release upon stimulation of non-canonical pathways, which is caused by caspase-11. Even at a 10 μM dose, MCC950 did not prevent Salmonella typhimurium-stimulated IL-1β and TNF-α production from NLRC4. When Salmonella enterica serovar Typhimurium is present, MCC950 does not prevent caspase-1 activation or IL-1β processing. Treatment with MCC950 basically has no effect on the production of pro-caspase-1 and pro-IL-1β in cell lysates [1].
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| ln Vivo |
MCC950 lessens the production of interleukin-1p (IL-1β) and lessens the severity of multiple sclerosis disease model experimental autoimmune encephalomyelitis (EAE). MCC950 pretreatment decreased serum levels of IL-1β and IL-6, but did not significantly lower TNF-α levels. Mice treated with MCC950 had a delayed onset of EAE and a decreased severity. Mice brain monocytes sacrificed on day 22 were subjected to intracellular cytokine staining and FACS analysis, which revealed that the MCC950-treated mice had more CD3+ T cells that produced IL-17 and IFN-γ than the PBS-treated mice. There is a slight decrease in frequency. The CD4+ and γδ+ subpopulations of CD3+ T cells also have a decrease in the number of cells generating IFN-γ, particularly IL-17 [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.
[2]. Zhai Y, et al. Inhibiting the NLRP3 Inflammasome Activation with MCC950 Ameliorates Diabetic Encephalopathy in db/db Mice. Molecules. 2018 Feb 27;23(3). pii: E522 |
| Molecular Formula |
C20H23N2O5S.NA
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|---|---|
| Molecular Weight |
426.46
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| CAS # |
256373-96-3
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| Related CAS # |
MCC950;210826-40-7
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| SMILES |
O=S(C1=CC(C(C)(O)C)=CO1)([N-]C(NC2=C3CCCC3=CC4=C2CCC4)=O)=O.[Na+]
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| 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
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| Synonyms |
CP-45677; CP45677; CP 45677; MCC950; MCC 950; MCC-950; CRID-3; CRID3; CRID 3; CP-456773 sodium
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| 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: ≥ 5 mg/mL (11.72 mM) (saturation unknown) in 5%DMSO 95%PBS (add these co-solvents sequentially from left to right, and one by one), clear solution.<
Solubility in Formulation 2: ≥ 2.5 mg/mL (5.86 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 (5.86 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: ≥ 2.08 mg/mL (4.88 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 20.8 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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 5: 2％DMSO 98％PBS Solubility in Formulation 6: 6.25 mg/mL (14.66 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3449 mL | 11.7244 mL | 23.4489 mL | |
| 5 mM | 0.4690 mL | 2.3449 mL | 4.6898 mL | |
| 10 mM | 0.2345 mL | 1.1724 mL | 2.3449 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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