| 名称 | Selisistat |
| 描述 | Selisistat (EX-527) is a potent and specific inhibitor of the deacetylase SIRT1 (IC50=38 nM). Selisistat can be used in the study of neurological disorders such as Huntington's chorea. |
| 细胞实验 | NCI-H460 cells, MCF-7 cells, U-2 OS cells, or HMEC were plated at 2,000 cells per well in opaque-walled 96-well plates for the viability assay and 800 cells per well in 96-well Cytostar-T scintillating microplates for the proliferation assay. Cells were incubated for 1 day (NCI-H460) or 2 days (MCF-7, U-2 OS, and HMEC) prior to exposure to DNA-damaging agents and deacetylase inhibitors. All experiments were performed in triplicate. For viability assays, cells were treated with the indicated compounds for 48 h. Cell viability was then determined using the Cell Titer-Glo luminescent assay, which measures total ATP levels as an index of cell number. Luminescence was measured on a Luminoskan Ascent. For the proliferation assay, 0.5 μCi/ml of [14C]thymidine was added to the medium immediately after the genotoxins and deacetylase inhibitors. Plates were counted at 48 h (HMEC) or 72 h (NCI-H460, MCF-7, and U-2 OS cells) in a Microbeta liquid scintillation counter. Thymidine incorporated by the cells was detected by proximity to the scintillant in the base of the Cytostar-T tissue culture plate [1]. |
| 动物实验 | Mice were injected with RSV (RSV) 30mg/kg (4ml/kg) or equivalent volume of DMSO (Vehicle) (4ml/kg) intraperitoneally 18 hours pre-sepsis. This dose of RSV in mice was as per documented literature. In one group of mice, RSV pre-treated mice received EX-527 (10 mg/kg intraperitoneally; 4ml/kg, Vehicle: DMSO) within 10 minutes of cecal ligation and puncture [5]. |
| 体外活性 | 方法：人结直肠癌细胞 HCT116 用 0.1% 血清和 Selisistat (1-2 µM) 培养 7 天，检测细胞数量。
结果：当 HCT116 细胞在 0.1% 血清中培养时，添加 Selisistat 导致 7 天后细胞数量增加 90%。在生长因子缺乏条件下，SirT1 是细胞增殖的重要调节因子。[1]
方法：人肺癌细胞 NCI-H460 用 etoposide (20 µM) 和 Selisistat (1 µM) 处理 6 h，使用 Western Blot 检测靶点蛋白表达水平。
结果：在用 DNA 损伤剂 etoposide 处理的细胞中，Selisistat 产生乙酰化 p53 的增加。[2] |
| 体内活性 | 方法：为研究对肺损伤的作用，将 Selisistat (10 mg/kg) 腹腔注射给 Balb/C 小鼠，0.5 h 后注射 LPS 诱导肝损伤。
结果：Selisistat 对 SIRT1 的选择性抑制可能部分通过抑制 mTOR 来减轻内毒素血症相关的急性肺损伤。[3]
方法：为研究对亨廷顿舞蹈症 (HD) 的作用，将 Selisistat (5-20 mg/kg，0.5% HPMC) 灌胃给药给 R6/2 小鼠，每天一次，直至死亡。
结果：Selisistat 治疗导致接受 20 mg/kg 剂量的小鼠的存活率显著增加，中位寿命显著增加了 3 周，在检查自主运动活动时也观察到显著的改善。[4] |
| 存储条件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | 10% DMSO+40% PEG300+5% Tween 80+45% Saline : 1.87 mg/mL (7.52 mM), Please add co-solvents sequentially, clarifying the solution as much as possible before adding the next one. Dissolve by heating and/or sonication if necessary. Working solution is recommended to be prepared and used immediately.
DMSO : 60 mg/mL (241.24 mM)
Ethanol : 12.4 mg/mL (50 mM)
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| 关键字 | mammalian | Huntington's | inhibit | pathology | Sirtuin | Drosophila | deacetylation | Selisistat | SEN-0014196 | EX 527 | Inhibitor | SEN 0014196 | disease | EX527 |
| 相关产品 | Fisetin | Nicotinamide riboside | Nicotinamide | Resveratrol | Dihydrocoumarin | Sirtinol | JGB1741 | SRT 2104 | Nicotinamide riboside chloride | 3-TYP | SIRT6-IN-5 | MC3482 |
| 相关库 | 经典已知活性库 | 高选择性抑制剂库 | 抗衰老化合物库 | 神经退行性疾病化合物库 | 药物功能重定位化合物库 | 抗癌药物库 |
