NLRP3-IN-8 (compound 27) 是具有口服活性的、与NLRP3直接结合的 NLRP3 炎性体抑制剂，对 IL-1 β 的IC50值为1.23 μM. NLRP3-IN-8 对肝微粒体具有良好的代谢稳定性 (t1/2= 138.63 min)，几乎没有毒性 (against L02: IC50>100 μM) 。

NLRP3-IN-8 (compound 27) is an orally active, directly binding NLRP3 inflammasome inhibitor with an IC 50 value of 1.23 μM against IL-1 β. NLRP3-IN-8 has good metabolic stability to liver microsomes (t 1/2 = 138.63 min), and has almost no toxicity (against L02: IC 50 >100 μM) [1].

NLRP3-IN-8 (compound 27) exhibits prominent anti-inflammatory activity with an IC 50 of 1.23 μM [1]. NLRP3-IN-8 exhibits good metabolic stability through human liver microsomes (t 1/2 = 138.63 min) [1]. NLRP3-IN-8 (0-10 μM, 1 h) significantly inhibits pyrolysis rate in a concentration-dependent manner [1]. NLRP3-IN-8 only inhibits the activation of NLRP3 inflammasomes, and could inhibit the activation of inflammasome by a variety of inducer [1]. NLRP3-IN-8 blocks NLRP3-induced ASC oligomerization [1]. NLRP3-IN-8 inhibits NLRP3 inflammasome assembly by blocking the interaction of NLRP3-NEK7 and NLRP3-ASC [1]. Western Blot Analysis [1] Cell Line: BMDMs cells Concentration: 0.5, 1, and 2 μM Incubation Time: 30 min, pretreated with LPS (200 ng/mL) for 3 h Result: Dose-dependently blocked IL-1 b secretion and caspase-1 cleavage at concentrations of 0.5-2 μM. Inhibited the maturation of intracellular caspase-1 (p20), and did not affect the expression of other constituent proteins of NLRP3 inflammasome, such as pro-IL-1 β, pro-caspase-1 (p45), NLRP3, ASC and NEK7.

NLRP3-IN-8 (compound 27) (DSS-induced C57BL/6 male mice; 0-20 mg/kg; intragastric; once a day, 7 days) effectively alleviates the severity of DSS-induced colitis in mouse [1]. Animal Model: DSS-induced acute colitis model in C57BL/6 male mice [1]. Dosage: 20 mg/kg and 10 mg/kg dissolved in 0.5% sodium carboxymethyl cellulose aqueous solution. Administration: Intragastric administration, once a day, 7 days. Result: Reduced the weight loss during the onset of colitis in mice, and decreased the disease activity index (DAI) in a dose-dependent manner. Reduced colon shortening, pathological index score, the expression of TNF-a, IL-6 and IL-1 β in the tissues and inhibited the decrease of goblet cells.

C23H20N2O6

420.41

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