NADPH oxidase-IN-1 是一种口服有效的NADPH氧化酶 (Nox) 抑制剂，与神经元炎症相关。NADPH oxidase-IN-1 可透过血脑屏障，抑制 Nox2 和 Nox4 的 IC50s 分别为 1.9 μM 和 2.47 μM。NADPH oxidase-IN-1 可抑制促炎细胞因子产生和 LPS 介导的小胶质细胞迁移，具有体内疗效。
| 生物活性 | NADPH oxidase-IN-1 is an orally activeNADPH oxidase(Nox) inhibitor, related with neuronal inflammation. NADPH oxidase-IN-1 can cross the blood-brain barrier (BBB), inhibitsNox2andNox4withIC50s 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]. |
| IC50& Target[1] | NOX2 1.9 μM (IC50) | NOX4 2.47 μM (IC50) |
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体外研究
(In Vitro) | NADPH oxidase-IN-1 (化合物11) 可以穿过血脑屏障，Pe值为 13.6 (10-6cm/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. |
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体内研究
(In Vivo) | 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 |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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