MCC950

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

MCC950 (CP-456773) 是一种有效的、选择性的 NLRP3 炎症小体小分子抑制剂，在 BMDM 和 HMDM 中的 IC50 分别为 7.5 和 8.1 nM。

MCC950 (CP-456773) is a potent, selective, small-molecule inhibitor of NLRP3 inflammasome with IC50 of 7.5 and 8.1 nM in BMDM and HMDM, respectively, specifically inhibits activation of NLRP3, does not inhibit NLRC4, AIM2, TLR signalling or priming of NLRP3; blocks NLRP3 induced ASC oligomerization, does not block K+ efflux, Ca2+ flux or NLRP3-ASC interactions; reduces interleukin-1β (IL-1β) production in vivo and attenuates the severity of experimental autoimmune encephalomyelitis (EAE), rescues neonatal lethality in mouse model of CAPS and is active in ex vivo samples from individuals with Muckle-Wells syndrome.

MCC950 blocks canonical and non-canonical NLRP3 activation at nanomolar concentrations. MCC950 specifically inhibits NLRP3 but not AIM2, NLRC4 or NLRP1 activation. The effect of MCC950 on NLRP3 inflammasome activation is tested in mouse bone marrow derived macrophages (BMDM) and human monocyte derived macrophages (HMDM). The IC50 of MCC950 in BMDM is approximately 7.5 nM, while in HMDM it has a similar inhibitory capacity (IC50=8.1 nM). 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.

MCC950 reduces Interleukin-1p (IL-1β) production and attenuates the severity of experimental autoimmune encephalomyelitis (EAE), a disease model of multiple sclerosis. Pre-treatment with MCC950 reduces serum concentrations of IL-1β and IL-6 while it does not considerably decrease the amount of TNF-α. 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.

MCC-950 | CP-456773

NF-κB

NOD

NLRP3

Inflammation/Immunology

——

210826-40-7

404.4799

C20H24N2O5S

>98% (HPLC)

DMSO: ≥ 28 mg/mL

CC(C)(C1=COC(=C1)S(=O)(=O)NC(=O)NC2=C3CCCC3=CC4=C2CCC4)O

2-Furansulfonamide, N-[[(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)amino]carbonyl]-4-(1-hydroxy-1-methylethyl)-

(-20℃)

With Ice Pack

≥ 2 years