CRID3 (CP-456773), Sodium Salt

产品描述：MCC950 sodium salt (IC50 of 7.5 nM in BMDMs) is an effective, selective NLRP3 inhibitor.

靶点活性：NLRP3,7.5nM

体外活性：MCC950 specifically inhibits NLRP3 activation,canonical NLRP3 activation in BMDM IC50 is of 7.5 ,and noncanonical NLRP3 activation in HMDM cells IC50 is of 8.1nM. MCC950 cannot inhibit activation of the AIM2, NLRC4 or NLRP1 inflammasomes.

体内活性:MCC950 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. [1]

细胞实验: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].

动物实验:C57BL/6 mice were injected intraperitoneally with 50 mg/kg MCC950.

动物模型：C57BL/6 mice

溶解度：DMSO: 42.7 mg/mL (100 mM)；water: 42.7 mg/mL (100 mM)（ < 1 mg/ml refers to the product slightly soluble or insoluble )