NADPH oxidase-IN-1

NADPH oxidase-IN-1 is an orally active NADPH Oxidase (Nox) inhibitor, related with neuronal inflammation. NADPH oxidase-IN-1 can cross the blood-brain barrier (BBB), inhibits Nox2 and Nox4 with IC50s of 1.9 μM and 2.47 μM, respectively. NADPH oxidase-IN-1 suppresses pro-inflammatory cytokines production and LPS-mediated microglial migration, also has in vivo efficacy[1].

Research Areas >> Neurological Disease

NOX2:1.9 μM (IC50)

NOX4:2.47 μM (IC50)

NADPH oxidase-IN-1 (化合物11) 可以穿过血脑屏障，Pe 值为 13.6 (10-6 cm/s)，由平行人工膜透性试验 (PAMPA) 测定[1]。 NADPH oxidase-IN-1 (1 nM-10 mM; 30min) 抑制 LPS 诱导 BV2 小胶质细胞产生 ROS，并呈剂量依赖性[1]。 NADPH oxidase-IN-1 (10 μM; 24 h) 抑制 BV2 细胞中促炎细胞因子的 mRNA 表达[1]。 NADPH oxidase-IN-1 (1 nM-10 mM; 24 h) 也抑制 BV2 细胞的激活和迁移[1]。 RT-PCR[1] Cell Line: BV2 microglial cells Concentration: 10 μM Incubation Time: 24 hours Result: Inhibited the mRNA expression of pro-inflammatory cytokines (iNOS, IL-1β, TNFα) in BV2 cells. Cell Migration Assay [1] Cell Line: BV2 microglial cells Concentration: 10 μM Incubation Time: 24 hours Result: Ameliorated inflammatory response and migration of microglia.

NADPH oxidase-IN-1 (化合物11) (30 mg/kg; 口服给药; 每日给药, 共 4 周) 在患帕金森疾病的小鼠模型中，能够减弱 MPTP 诱导的小胶质细胞激活，减少多巴胺能神经元损伤[1]。 NADPH oxidase-IN-1 通过静脉注射 (10-300 mg/kg; 单次给药) 和灌胃 (10- 1000mg /kg;单次剂量) 处理，对雄性和雌性小鼠都是安全的[1]。 在大鼠中的药代动力学特征 Parameters C0 (μg/mL) Cmax (μg/mL) t1/2 (h) Tmax (h) AUClast (μg/h/mL) ke (1/h) Vd (L) Vd/F (L) Cl (L/h) Cl/F (L/h) F (%) IV (2 mg/kg) 1.70 0.79 0.468 1.32 0.211 0.217 PO (10 mg/kg) 0.609 5.01 [0.083-2] 1.31 0.170 1.99 0.341 56.0 PO (20 mg/kg) 0.783 6.13 [0.67-2] 4.16 0.159 1.82 0.217 88.9

[1]. Shim S, et al. Discovery of a NADPH oxidase inhibitor,(E)-3-cyclohexyl-5-(4-((2-hydroxyethyl)(methyl) amino) benzylidene)-1-methyl-2-thioxoimidazolidin-4-oneone, as a novel therapeutic for Parkinson's disease[J]. European Journal of Medicinal Chemistry, 2022, 244: 114854.