NLRP3-IN-14

NLRP3-IN-14 is a potent and selective NLRP3 inflammasome inhibitor (KD: 5.87 μM). NLRP3-IN-14 inhibits IL-1β release with an IC50 of 0.131 μM. NLRP3-IN-14 can be used for the research of inflammation[1].

Signaling Pathways >> Immunology/Inflammation >> NOD-like Receptor (NLR)

Research Areas >> Inflammation/Immunology

NLRP3 inflammasome:5.87 μM (Kd)

NLRP3-IN-14 (化合物 5j) 抑制 IL-1β 释放，IC50 为 0.131 μM (ELISA 测定) [1]。 NLRP3-IN-14 (2 μM，3 小时) 抑制小鼠腹膜巨噬细胞 (PM) 中 IL-1β (p17) 和 caspase-1 (p20) 的分泌[1]。 NLRP3-IN-14 通过抑制 ASC 寡聚化来抑制 NLRP3 炎性体复合物的形成[1]。 NLRP3-IN-14 (10 μM，5 小时) 随着温度升高抑制蛋白质 NLRP3 的降解[1]。 NLRP3-IN-14 在人和小鼠肝微粒体中表现出代谢稳定性 (T1/2: 866.3 min; Clint: 1.6 μL/min/mg)[1]. Western Blot Analysis[1] Cell Line: Mice peritoneal macrophages(PMs) Concentration: 2 μM Incubation Time: 3 h Result: Inhibited the secretion of IL-1β (p17) and caspase-1 (p20), without affecting pro-IL-1β and pro-caspase-1.

NLRP3-IN-14 (化合物 5j) (50 mg/kg;i.p.) 在败血症小鼠模型中表现出抗炎作用[1]。 Animal Model: LPS-induced inflammatory septic mouse model[1] Dosage: 50 mg/kg Administration: i.p. Result: Decreased the release of IL-1β in mouse serum. Relieved thickening of the alveolar wall in lung. Animal Model: Mice[1] Dosage: 20 or 5 mg/kg Administration: p.o. or i.v. Result: Pharmacokinetic profile of NLRP3-IN-14 (compound 5j). parameter dose (mg/kg) T1/2 (h) Tmax (h) F (%) PO 20 9.225 0.389 3.0 IV 5 5.028 0.083

[1]. Li J, et al. Scaffold Hybrid of the Natural Product Tanshinone I with Piperidine for the Discovery of a Potent NLRP3 Inflammasome Inhibitor. J Med Chem. 2023 Feb 23;66(4):2946-2963.