GSK2795039
目录号 : GC32681
GSK2795039是一种强效NADPH氧化酶2（NOX2）抑制剂，IC50值为0.18μM。
Cas No.:1415925-18-6
Sample solution is provided at 25 µL, 10mM.
GSK2795039 is a potent inhibitor of NADPH oxidase 2 (NOX2) enzyme with an IC50 value of 0.18μM[1]. GSK2795039 showed antiviral activity against H1N1 influenza A virus both in vitro and in vivo[2]. GSK2795039 has been extensively used to inhibit reactive oxygen species (ROS) formation and utilization of the enzyme substrates NADPH and oxygen in cellular, mouse, and rat models[3].
In vitro, GSK2795039 treatment (25μM) for 24h significantly inhibited cell death of in the presence of 10uM amyloid-beta (Aβ) and reduced Aβ-induced ROS production[4]. Treatment with 20μM GSK2795039 for 16h reversed the enhanced reductive carboxylation in A549 cells after rotenone treatment[5]. GSK2795039 treatment at 100μM for 24 hours increased the phosphorylation of p38-MAPK and inhibited cell viability in FLT3-mutant MV4-11 cells[6].
In vivo, GSK2795039 treatment via twice-daily intragastric gavage (2.5mg/kg) for 38 days improved survival and left ventricular function, suppressed protein expression of Nox2, p22phox, p47phox and p67phox, and alleviated myocardial oxidative stress in mice with doxorubicin-induced cardiomyopathy[7]. Intraperitoneal injection of GSK2795039 at a dose of 100mg/kg/day for 15 days improved cardiac dysfunction and cardiac remodeling and reduced cardiomyocyte apoptosis and collagen deposition in a mouse model of myocardial infarction[8].
References:
[1] Mason H, Rai G, Kozyr A, et al. Development of an improved and specific inhibitor of NADPH oxidase 2 to treat traumatic brain injury[J]. Redox Biology, 2023, 60: 102611.
[2] Xue N, Wang L, Wang B, et al. NOX2 oxidase inhibitor GSK2795039 possess antiviral activity against H1N1 influenza A virus in vitro and vivo[J]. Microbial Pathogenesis, 2023, 174: 105942.
[3]Hirano K, Chen W S, Chueng A L W, et al. Discovery of GSK2795039, a novel small molecule NADPH oxidase 2 inhibitor[J]. Antioxidants & redox signaling, 2015, 23(5): 358-374.
[4] Potapov K V, Platonov D N, Belyy A Y, et al. Improved Synthesis of Effective 3-(Indolin-6-yl)-4-(N-pyrazole-sulfonamide)-1 H-pyrrolo [2, 3-b] pyridine-Based Inhibitors of NADPH Oxidase 2[J]. International Journal of Molecular Sciences, 2025, 26(8): 3647.
[5] Zhang R, Chen D, Fan H, et al. Cellular signals converge at the NOX2-SHP-2 axis to induce reductive carboxylation in cancer cells[J]. Cell chemical biology, 2022, 29(7): 1200-1208. e6.
[6] Germon Z P, Sillar J R, Mannan A, et al. Blockade of ROS production inhibits oncogenic signaling in acute myeloid leukemia and amplifies response to precision therapies[J]. Science Signaling, 2023, 16(778): eabp9586.
[7] Zhang X J, Li L, Wang A L, et al. GSK2795039 prevents RIP1-RIP3-MLKL-mediated cardiomyocyte necroptosis in doxorubicin-induced heart failure through inhibition of NADPH oxidase-derived oxidative stress[J]. Toxicology and applied pharmacology, 2023, 463: 116412.
[8] Liu Y, Wu Z, Ji M, et al. NADPH oxidase 2 inhibitor GSK2795039 prevents against cardiac remodeling after MI through reducing oxidative stress and mitochondrial dysfunction[J]. European Journal of Pharmacology, 2025, 997: 177483.
GSK2795039是一种强效NADPH氧化酶2（NOX2）抑制剂，IC50值为0.18μM[1]。GSK2795039在体外和体内均表现出抗甲型H1N1流感病毒的活性[2]。GSK2795039广泛应用于细胞、小鼠和大鼠模型中抑制活性氧（ROS）生成及酶底物NADPH和氧的消耗[3]。
在体外，25μM的GSK2795039处理24小时可显著抑制10μM的β-淀粉样蛋白（Aβ）诱导的细胞死亡，并减少Aβ触发的ROS产生[4]。20μM的GSK2795039处理16小时能逆转鱼藤酮处理后A549细胞中增强的还原羧化作用[5]。100μM的GSK2795039处理FLT3突变的MV4-11细胞24小时可增加p38-MAPK磷酸化并抑制细胞活力[6]。
在体内，多柔比星诱导的心肌病小鼠每日两次胃内灌服GSK2795039（2.5mg/kg；持续38天）可提高生存率和左心室功能，抑制Nox2、p22phox、p47phox和p67phox蛋白表达，并减轻心肌氧化应激[7]。心肌梗死小鼠模型每日腹腔注射100mg/kg剂量的GSK2795039（持续15天）能改善心功能障碍和心脏重构，减少心肌细胞凋亡和胶原沉积[8]。
| Cell experiment [1]: | |
Cell lines | HMC3 cell |
Preparation Method | HMC3 cells were cultured in minimal essential medium (MEM) containing 10% fetal bovine serum, 100U/mL penicillin, 100µg/mL streptomycin, sodium pyruvate, and glutamate. Cells were grown at 37°C in a humidified atmosphere with 5% CO2. HMC3 cells were seeded in 12-well plates and cultured at 37°C for 24 hours. Cells were then treated with Aβ (10µM) in the presence and absence of GSK2795039 (25µM) for 24h, followed by incubation with DHR dye for 15min at 37°C in the dark. Then, the cells were incubated with 10μg/mL propidium iodide (PI) for 1min before flow cytometry analysis. |
Reaction Conditions | 25µM; 24h |
Applications | GSK2795039 treatment reduced the cell death of HMC3 cells caused by Aβ. |
| Animal experiment [2]: | |
Animal models | Male C57BL/6J mice |
Preparation Method | Eight-week-old male C57BL/6J mice were randomly divided into three experimental groups: (1) control group (n=9), mice received normal saline (NS)(i.p.); (2) Doxorubicin (DOX) group (n=22), mice received DOX intraperitoneal injection at a cumulative dose of 15mg/kg (2.5mg/kg; once every other day for 6 times); (3) DOX plus GSK2795039 group (n=19), mice received intraperitoneal injection of DOX 15mg/kg (2.5mg/kg; once every other day for 6 times) and intragastric gavage of GSK 2.5mg/kg (twice a day for 38 days) from the second day after DOX injection. Mouse survival rate was recorded, and mouse heart samples were collected for analysis. |
Dosage form | 2.5mg/kg twice a day for 38 days; i.g. |
Applications | GSK2795039 treatment improved survival and left ventricular function in mice with DOX-induced cardiomyopathy. |
References: | |
| Cas No. | 1415925-18-6 | SDF | |
| Canonical SMILES | CC(C)N1C=C(C2=CC=C(CCN3C)C3=C2)C4=C1N=CC=C4NS(C5=NN(C)C=C5)(=O)=O | ||
| 分子式 | C23H26N6O2S | 分子量 | 450.56 |
| 溶解度 | DMSO : ≥ 32 mg/mL (71.02 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2195 mL | 11.0973 mL | 22.1946 mL |
| 5 mM | 443.9 μL | 2.2195 mL | 4.4389 mL |
| 10 mM | 221.9 μL | 1.1097 mL | 2.2195 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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