GLX351322 is a NADPH Oxidase 4 (NOX4) inhibitor, with an IC50 value of 5μM [1]. GLX351322 inhibits ROS/MAPK/NF-κB signaling pathways, exhibiting anti-inflammatory effect[2]. GLX351322 has been widely used in various animal models to regulate neural functions and reduce oxidative stress[3].
In vitro, GLX351322 (10μM) treatment for 3 hours reduced the production of reactive oxygen species (ROS) and cell death in human islet cells induced by high glucose and palmitate[4]. Treatment with 40μM GLX351322 for 24 hours inhibited the proliferation of hypoxia-induced leiomyoma cells and promoted cell apoptosis[5]. Treatment with 5μM GLX351322 for 48 hours enhanced the cell death of BCPAP and TPC-1 cells treated with Lenvatinib[6].
In vivo, GLX351322 treatment via oral administration at a dose of 3.8mg/kg/day for 2 weeks suppressed tumor growth and progression in Gl261 glioma cell-intracranial xenograft mice [7]. Continuous intraperitoneal injection of 5mg/kg/day dose of GLX351322 for four consecutive weeks rescued synaptic and memory deficits, and decreased oxidative stress and amyloid levels in the hippocampus of APP/PS1 mice [8].
References:
[1] Anvari E, Wikström P, Walum E, et al. The novel NADPH oxidase 4 inhibitor GLX351322 counteracts glucose intolerance in high-fat diet-treated C57BL/6 mice[J]. Free radical research, 2015, 49(11): 1308-1318.
[2] Zhen J, Chen X, Mao Y, et al. GLX351322, a Novel NADPH Oxidase 4 Inhibitor, Attenuates TMJ Osteoarthritis by Inhibiting the ROS/MAPK/NF‐κB Signaling Pathways[J]. Oxidative Medicine and Cellular Longevity, 2023, 2023(1): 1952348.
[3] Kaur S, Verma R, Sharma V, et al. Targeting NOX inhibitors in neurodegeneration: a therapeutic perspective[J]. Metabolic Brain Disease, 2025, 40(5): 219.
[4] Wang X, Elksnis A, Wikström P, et al. The novel NADPH oxidase 4 selective inhibitor GLX7013114 counteracts human islet cell death in vitro[J]. PLoS One, 2018, 13(9): e0204271.
[5] Miyashita-Ishiwata M, El Sabeh M, Reschke L D, et al. Hypoxia induces proliferation via NOX4-Mediated oxidative stress and TGF-β3 signaling in uterine leiomyoma cells[J]. Free radical research, 2022, 56(2): 163-172.
[6] Tang P, Sheng J, Peng X, et al. Targeting NOX4 disrupts the resistance of papillary thyroid carcinoma to chemotherapeutic drugs and lenvatinib[J]. Cell Death Discovery, 2022, 8(1): 177.
[7] Jiang H, Li F, Cai L, et al. Role of the TSPO–NOX4 axis in angiogenesis in glioblastoma[J]. Frontiers in Pharmacology, 2022, 13: 1001588.
[8] Tao W, Yu L, Shu S, et al. miR-204-3p/Nox4 mediates memory deficits in a mouse model of Alzheimer’s disease[J]. Molecular Therapy, 2021, 29(1): 396-408.
GLX351322是一种NADPH氧化酶4 (NOX4)抑制剂，IC50值为5μM[1]。GLX351322通过抑制ROS/MAPK/NF-κB信号通路发挥抗炎作用[2]。GLX351322已广泛应用于多种动物模型中调节神经功能及减轻氧化应激[3]。
在体外，使用10μM的GLX351322处理人胰岛细胞3小时，可减少高糖和棕榈酸诱导的活性氧(ROS)生成及细胞死亡[4]。用40μM的GLX351322处理平滑肌瘤细胞24小时，能抑制缺氧诱导的细胞增殖并促进凋亡[5]。以5μM的GLX351322处理BCPAP和TPC-1细胞48小时，可增强乐伐替尼诱导的细胞死亡[6]。
在体内，每日口服3.8mg/kg剂量的GLX351322连续2周，能抑制Gl261胶质瘤颅内移植瘤小鼠的肿瘤生长与进展[7]。连续4周每日腹腔注射5mg/kg/day剂量的GLX351322，可挽救APP/PS1小鼠的突触与记忆缺陷，并降低海马区氧化应激水平和淀粉样蛋白沉积[8]。