Dicoumarol
(Synonyms: 双香豆素; Dicumarol) 目录号 : GC15350
A competitive NQO1 inhibitor
Cas No.:66-76-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | The in vitro cell viability is examined using the standard MTT assay. SKOV3 or A2780 cells are seeded in 96-well plates at 8000 cells/well. The next day, increasing concentrations of Dicoumarol (DIC) are added into each well, and the plate is incubated for 24 h. Then, 10 μL of 10 mg/mL MTT reagent in phosphate-buffered saline (PBS) is added into each well, and the plate is incubated for an additional 4 h. The formazan crystals are dissolved in 150 μL of DMSO, and after the plate is shaken for 5 min, the optical density at 570 nm is recorded by the reader[2]. |
Animal experiment: | Twenty five female BALB/c-nu mice aged 5 to 6 weeks old and weighing approximately 15 g each are used. A total of 1×107 SKOV3 cells are subcutaneously injected into the upper flank. After 10 days, when the tumor volume reaches approximately 100 mm3, the nude mice are randomized into five groups (n=5/group) and are given the following treatments intraperitoneally (i.p.) every other day, for a total of 12 days: control group, administered with 0.2 mL of 0.9% NaCl; vehicle group, administered with 1 mM NaOH; dichloroacetate (DCA) group, administered with 100 mg/kg DCA; Dicoumarol (DIC)-30 group, administered with 30 mg/kg Dicoumarol; and Dicoumarol-50 group, administered with 50 mg/kg Dicoumarol. The body weights and tumor volumes of each mouse are monitored every other day until sacrifice (on day 12 after the initial treatment)[2]. |
References: [1]. Bian J, et al. Affinity-based small fluorescent probe for NAD(P)H:quinone oxidoreductase 1 (NQO1). Design, synthesis and pharmacological evaluation. Eur J Med Chem. 2017 Feb 15;127:828-839. | |
Dicoumarol is an inhibitor of both NAD(P)H:quinone oxidoreductase 1 (NQO1) and PDK1 with IC50s of 0.37 and 19.42 μM, respectively.
Dicoumarol is an inhibitor of both NAD(P)H:quinone oxidoreductase 1 (NQO1) and PDK1 with IC50s of 0.37±0.15 and 19.42±0.032 μM, respectively. The PDK1 activity is inhibited by Dicoumarol in a dose-dependent manner. The enzymatic activity of PDK1 is reduced by approximately 94% when treated with 200 μM Dicoumarol. Dicoumarol decreases the p-PDHA1 level by 26% (100 μM Dicoumarol) and by 72% (200 μM Dicoumarol), with no statistical difference in the total PDHA1 level. Both 100 μM and 200 μM Dicoumarol markedly induce apoptosis of SKOV3 cells. Similarly, flow cytometric analysis of annexin V+PI+ cells reveals that 100 μM and 200 μM Dicoumarol treatments generate approximately 20.87% and 24.94% apoptotic cells, respectively, significantly higher than vehicle treatment[2]. It is also observed that treatment of MCF-7-TAMR cells with Dicoumarol, a known NQO1 inhibitor, reverses their tamoxifen-resistance phenotype[3].
Dichloroacetate (DCA) at 100 mg/kg, Dicoumarol at 30 mg/kg, and Dicoumarol at 50 mg/kg all significantly reduce tumor volume and decrease tumor weight, when compare to tumors from control or vehicle groups. Total caspase-3 and total anti-poly (ADP-ribose) polymerase (PARP) are significantly decreased in Dicoumarol-treated SKOV3 xenografts, when compare to tumors from the control or vehicle group[2].
References:
[1]. Bian J, et al. Affinity-based small fluorescent probe for NAD(P)H:quinone oxidoreductase 1 (NQO1). Design, synthesis and pharmacological evaluation. Eur J Med Chem. 2017 Feb 15;127:828-839.
[2]. Zhang W, et al. Dicumarol inhibits PDK1 and targets multiple malignant behaviors of ovarian cancer cells. PLoS One. 2017 Jun 15;12(6):e0179672.
[3]. Fiorillo M, et al. Mitochondrial "power" drives tamoxifen resistance: NQO1 and GCLC are new therapeutic targets in breast cancer. Oncotarget. 2017 Mar 2;8(12):20309-20327.
| Cas No. | 66-76-2 | SDF | |
| 别名 | 双香豆素; Dicumarol | ||
| 化学名 | 3,3'-methylenebis(4-hydroxy-2H-chromen-2-one) | ||
| Canonical SMILES | OC(C1=CC=CC=C1OC2=O)=C2CC3=C(O)C4=CC=CC=C4OC3=O | ||
| 分子式 | C19H12O6 | 分子量 | 336.29 |
| 溶解度 | DMF: 1.25 mg/ml,DMSO: 2.5 mg/ml,DMSO:PBS (pH 7.2) (1:1): 0.5 mg/ml,Ethanol: slight solubility | 储存条件 | Desiccate 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 | 2.9736 mL | 14.8681 mL | 29.7362 mL |
| 5 mM | 0.5947 mL | 2.9736 mL | 5.9472 mL |
| 10 mM | 0.2974 mL | 1.4868 mL | 2.9736 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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