MCC950-sodium-CP-456773-sodium-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEMCC950 sodiumCat. No.: HY-12815ACAS No.: 256373-96-3Synonyms: CP-456773 sodium; CRID3 sodium salt分式: CHNNaOS分量: 426.46作靶點: NOD-like Receptor (NLR)作通路: Immunology/Inflammation儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 mo

2、nths-20C 1 month溶解性數(shù)據(jù)體外實驗 H2O : 30 mg/mL (70.35 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.3449 mL 11.7244 mL 23.4489 mL5 mM 0.4690 mL 2.3449 mL 4.6898 mL10 mM 0.2345 mL 1.1724 mL 2.3449 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。體內(nèi)實驗 MCC950 so

3、dium is prepared in PBS2.BIOLOGICAL ACTIVITY物活性 MCC950 sodium種有效，選擇性的 NLRP3 抑制劑，在BMDMs 和 HMDMs中的 IC50 分別為 7.5 nM 和 8.1nM。1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEIC50 & Target IC50: 7.5 nM (NLRP3, in BMDMs), 8.1 nM (NLRP3, in HMDMs) 1體外研究 MCC950 blocks canonical and non-canonical NLRP3 activ

4、ation at nanomolar concentrations. MCC950specifically inhibits NLRP3 but not AIM2, NLRC4 or NLRP1 activation. The effect of MCC950 on NLRP3inflammasome activation is tested in mouse bone marrow derived macrophages (BMDM) and humanmonocyte derived macrophages (HMDM). The IC50 of MCC950 in BMDM is app

5、roximately 7.5 nM, while inHMDM it has a similar inhibitory capacity (IC50=8.1 nM). MCC950 also dose dependently inhibit IL-1 but notTNF- secretion.MCC950 specifically blocks caspase-11-directed NLRP3 activation and IL-1 secretionupon stimulation of the non-canonical pathway. NLRC4-stimulated IL-1 a

6、nd TNF- secretion (as activatedby Salmonella typhimurium) are not inhibited by MCC950 even at a concentration of 10 M. MCC950 doesnot inhibit caspase-1 activation or IL-1 processing in response to S. typhimurium. The expression of pro-caspase-1 and pro-IL-1 in cell lysates is not substantially affec

7、ted by MCC950 treatment 1.體內(nèi)研究 MCC950 reduces Interleukin-1p (IL-1) production and attenuates the severity of experimental autoimmuneencephalomyelitis (EAE), a disease model of multiple sclerosis. Pre-treatment with MCC950 reduces serumconcentrations of IL-1 and IL-6 while it does not considerably d

8、ecrease the amount of TNF-. Treatment ofmice with MCC950 delays the onset and reduced the severity of EAE. Intracellular cytokine staining andFACS analysis of brain mononuclear cells from mice sacrificed on day 22 shows modestly reducedfrequencies of IL-17 and IFN- producing CD3+ T cells in MCC950 t

9、reated mice in comparison with PBS-treated mice. IFN- and particularly IL-17 producing cell numbers are also reduced in both the CD4+ and +sub-populations of CD3+ T cells 1.PROTOCOLCell Assay 1 BMDM are seeded at 5105/mL or 1106/mL, HMDM at 5105/mL and PBMC at 2106/mL or 5106/mL in96 well plates. Th

10、e following day the overnight medium is replaced and cells are stimulated with 10 ng/mLLPS from Escherichia coli serotype EH100 (ra) TLRgrad for 3 h. Medium is removed and replaced withserum free medium (SFM) containing DMSO (1:1,000), MCC950 (0.001-10 M), glyburide (200 M),Parthenolide (10 M) or Ba

11、yer cysteinyl leukotriene receptor antagonist 1-(5-carboxy-23-4-(3-cyclohexylpropoxy)phenylpropoxybenzoyl)piperidine-4-carboxylic acid (40 M) for 30 min. Cells are thenstimulated with inflammasome activators: 5 mM adenosine 5-triphosphate disodium salt hydrate (ATP) (1 h),1 g/mL Poly(deoxyadenylic-t

12、hymidylic) acid sodium salt (Poly dA:dT) transfected with Lipofectamine 200 (3-4 h), 200 g/mL MSU (overnight) and 10 M nigericin (1 h) or S. typhimurium UK-1 strain. Cells are alsostimulated with 25 g/mL Polyadenylic-polyuridylic acid (4 h). For non-canonical inflammasome activationcells are primed

13、with 100 ng/mL Pam3CSK4 for 4 h, medium is removed and replaced with SFM containingDMSO or MCC950 and 2 g/mL LPS is transfected using 0.25% FuGENE for 16 h. Supernatants areremoved and analysed using ELISA kits. LDH release is measured using the CytoTox96 non-radioactivecytotoxicity assay 1.MCE has

14、not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 1Administration 1 C57BL/6 mice are immunized subcutaneously with 150 g of MOG peptide 35-55 emulsified in CFAcontaining 4 mg/mL (0.4.mg/mouse) of heat-killed MTB. Mice are injected i.p. with 500 ng per

15、tussis toxin (PT:2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEkaketsuken) 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 timepoints. Mice are observed

16、for clinical signs of disease daily (unblinded). Disease severity is scored asfollows: no clinical signs, 0; limp tail, 1; ataxic gait, 2; hind limb weakness, 3; hind limb paralysis, 4; and tetraparalysis, 5.MCE has not independently confirmed the accuracy of these methods. They are for reference on

17、ly.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Cell Mol Immunol. 2019 Jul 18. Redox Biol. 2019 Jun 7. Cell Death Dis. 2018 Sep 20;9(10):946. Cell Death Dis. 2017 Nov 16;8(11):e3170. J Neuroinflammation. 2018 Mar 24;15(1):95.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Coll RC, et al. A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nat Med. 2015Mar;21(3):248-55.2. Zhai Y, et al. Inhibiting the NLRP3 Inflammasome Activation with MCC950 Ameliorates Diabetic En