Digoxin
(Synonyms: 地高辛,12β-Hydroxydigitoxin) 目录号 : GC13108
地高辛（Digoxin）是一种强效的Na+/K+-ATP酶抑制剂，临床用于治疗心律失常和心力衰竭。
Cas No.:20830-75-5
Sample solution is provided at 25 µL, 10mM.
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| Cell experiment [1]: | |
Cell lines | A549 and H1299 cells |
Preparation Method | Cells (3×104 cells/mL) were cultured in a 96-well plate treated with various concentrations of digoxin(0-1µM) for 24h or 48h. After addition of MTT (5mg/mL) to each well, the cells were further incubated for 4h. |
Reaction Conditions | 0-1µM; 24 or 48h |
Applications | Digoxin inhibited proliferation of A549 and H1299 cells in a dose-dependent manner, with IC50 values of 0.10 and 0.12µM for A549 and H1299 cells, respectively. |
| Animal experiment [2]: | |
Animal models | Male BALB/c nude mice |
Preparation Method | 2×106 Raji cells (100μL 1640 medium and matrigel mixture) were injected subcutaneously into the right flank of four-week-old male BALB/c nude mice, two days after mice were injected intraperitoneally with cyclophosphamide (75mg/kg) to suppress xenograft rejection. When the tumor volume reached 50mm3, the animals were randomized into control and treatment groups. Within three weeks, the animals were injected intraperitoneally with digoxin (2mg/kg/day) or vehicle. The tumor volume and body weight of the mice were monitored twice a week. Mice were killed after 20 days of treatment. Tumors were collected and fixed with 4% paraformaldehyde for hematoxylin-eosin and immunohistochemistry (IHC). |
Dosage form | 2mg/kg; i.p. |
Applications | Digoxin inhibited the tumor volume by 66.2% with no obvious toxicity to mice and no change in body weight. Digoxin reduced the distribution of Raji cells in tumor tissues. Digoxin reduced the expression of Ki-67 and c-myc proteins. |
References: | |
Digoxin is a potent Na+/K+-ATPase inhibitor clinically used to treat arrhythmias and heart failure[1]. Digoxin belongs to the class of digitalis glycosides, which are used to increase cardiac strength and efficiency, or to control heart rate and rhythm[2]. Digoxin is a specific inhibitor of the transcriptional activity of the retinoic acid receptor-related orphan nuclear receptor RORγt[3].
In vitro, treatment of A549 and H1299 cells with Digoxin (0-1µM) for 24 or 48h inhibited the proliferation of A549 and H1299 cells in a dose-dependent manner, with IC50 values of 0.10 and 0.12μM, respectively, and also induced DNA damage and increased ROS production[4]. Digoxin (1µM) treatment of T84 epithelial cells for 72h effectively induced P-glycoprotein MDR1 transcription level (92-fold), total protein (7-fold), apical MDR1 protein (4.7-fold) and functional activity (1.75-fold)[5].
In vivo, Digoxin (2mg/kg) treated by intraperitoneal injection for 20 days in mice transplanted with Raji cells inhibited 66.2% of tumor volume, had no obvious toxic effects on mice, reduced the distribution of Raji cells in tumor tissues, and reduced the expression of Ki-67 and c-myc proteins [6]. Digoxin (1, 2mg/kg) treated by intraperitoneal injection for 14 days in mice with experimental autoimmune uveitis (EAU) inhibited the development of EAU and the cellular immune response to inter-photoreceptor retinoid acid binding protein (IRBP), but caused severe damage to the retina[7].
References:
[1] Ashbrook A W, Lentscher A J, Zamora P F, et al. Antagonism of the sodium-potassium ATPase impairs chikungunya virus infection[J]. MBio, 2016, 7(3): 10.1128/mbio. 00693-16.
[2] Ibrahim N A M. An up-to-date review of digoxin toxicity and its management[J]. Int. J. Res. Pharm. Pharm. Sci, 2019, 4: 59-64.
[3] Huh J R, Leung M W L, Huang P, et al. Digoxin and its derivatives suppress TH17 cell differentiation by antagonizing RORγt activity[J]. Nature, 2011, 472(7344): 486-490.
[4] Wang Y, Ma Q, Zhang S, et al. Digoxin enhances the anticancer effect on non-small cell lung cancer while reducing the cardiotoxicity of adriamycin[J]. Frontiers in pharmacology, 2020, 11: 186.
[5] Haslam I S, Jones K, Coleman T, et al. Rifampin and digoxin induction of MDR1 expression and function in human intestinal (T84) epithelial cells[J]. British journal of pharmacology, 2008, 154(1): 246-255.
[6] Wang T, Xu P, Wang F, et al. Effects of digoxin on cell cycle, apoptosis and NF-κ B pathway in Burkitt’s lymphoma cells and animal model[J]. Leukemia & Lymphoma, 2017, 58(7): 1673-1685.
[7] Hinshaw S J H, Ogbeifun O, Wandu W S, et al. Digoxin inhibits induction of experimental autoimmune uveitis in mice, but causes severe retinal degeneration[J]. Investigative ophthalmology & visual science, 2016, 57(3): 1441-1447.
地高辛（Digoxin）是一种强效的Na+/K+-ATP酶抑制剂，临床用于治疗心律失常和心力衰竭[1]。Digoxin属于洋地黄糖苷类药物，它用于提高心脏的力量和效率，或控制心跳的速率和节律[2]。Digoxin是视黄酸受体相关的孤儿核受体RORγt转录活性的特异性抑制剂[3]。
在体外，Digoxin（0-1µM）处理A549和H1299细胞24或48h，以剂量依赖性方式抑制A549和H1299细胞的增殖，IC50值分别为0.10和0.12μM，还诱导了DNA损伤，增加了ROS产生[4]。Digoxin（1µM）处理T84 上皮细胞72h，可有效诱导P-糖蛋白MDR1转录水平（92 倍）、总蛋白（7倍）、顶端MDR1 蛋白（4.7倍）和功能活性（1.75倍）[5]。
在体内，Digoxin（2mg/kg）通过腹腔注射治疗移植了Raji细胞的小鼠20天，抑制了66.2%的肿瘤体积，对小鼠没有明显的毒性作用，减少了肿瘤组织中 Raji细胞的分布，减少了Ki-67和c-myc蛋白的表达[6]。Digoxin（1、2mg/kg）通过腹腔注射治疗实验性自身免疫性葡萄膜炎（EAU）小鼠14天，抑制了EAU 的发展和对光感受器间类视黄酸结合蛋白（IRBP）的细胞免疫反应，但是对视网膜造成了严重损伤[7]。
| Cas No. | 20830-75-5 | SDF | |
| 别名 | 地高辛,12β-Hydroxydigitoxin | ||
| Canonical SMILES | O[C@]1([C@]([C@@H](C2=CC(OC2)=O)CC1)(C)[C@@H]3O)[C@H]4[C@H](C3)[C@](CC[C@@H]5O[C@@H](C[C@@H]6O)O[C@H](C)[C@H]6O[C@@H](C[C@@H]7O)O[C@H](C)[C@H]7O[C@@H](C[C@@H]8O)O[C@H](C)[C@H]8O)(C)[C@@H](C5)CC4 | ||
| 分子式 | C41H64O14 | 分子量 | 780.94 |
| 溶解度 | ≥ 33.25mg/mL in DMSO | 储存条件 | 4°C, protect from light |
| 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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1 mg | 5 mg | 10 mg |
| 1 mM | 1.2805 mL | 6.4025 mL | 12.8051 mL |
| 5 mM | 0.2561 mL | 1.2805 mL | 2.561 mL |
| 10 mM | 0.1281 mL | 0.6403 mL | 1.2805 mL |
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