Disulfiram   中文名称: 双硫仑

双硫仑-铜复合物在导致癌细胞凋亡之前，可有效降低培养的乳腺癌 MDA-MB-231 和 MCF10DCIS.com 细胞中的蛋白酶体活性，但不会降低正常永生化 MCF-10A 细胞中的蛋白酶体活性 [1]。商业上使用的抗酒精药物双硫仑 (DS) 可显着且剂量依赖性地抑制结构性和 5-FU 诱导的 NF 激活。 DisuLfiram 对 5-FU 诱导的 IkappaBalpha 降解几乎没有影响，尽管它确实降低了 NF-kappaB 核易位和 DNA 结合活性。双硫仑协同增加 5-FU 对 DLD-1 和 RKO (WT) 细胞系的细胞毒性，同时还显着增强 5-FU 对这些细胞系的凋亡作用。此外，DisuLfiram 在体外成功消除了 5-FU 耐药细胞系 H630 (5-FU) 中的 5-FU 化疗耐药性 [2]。 CuCl2 极大地增加了 DSF 诱导的细胞死亡，使其低于对照的 10%，而奥司他韦则减少了活细胞的数量 [3]。在比单独使用双硫仑更低的浓度下，双硫仑与黑色素瘤细胞中的 Cu2+ 或 Zn2+ 组合可降低细胞周期蛋白 A 的表达并抑制体外增殖 [4]。 DisuLfiram（0.1 nM-10 μM；72 小时）和 Cu2+ 的组合可增加其对卵巢癌细胞系的细胞毒性 [1]。

双硫仑显着减少含有 MDA-MB-231 肿瘤异种移植物的小鼠的肿瘤发展 (74%)；这与蛋白酶体抑制和细胞凋亡诱导有关[1]。在肿瘤组织中，泛素化蛋白和天然蛋白酶体底物p27和Bax积累，这些蛋白酶体抑制指标用于衡量蛋白酶体抑制的程度。 Caspases 被激活和凋亡细胞核形成是细胞凋亡的标志[1]。双硫仑抑制核因子-kappaB 转录因子，限制 P-糖蛋白挤出泵，减少血管生成，使肿瘤对化疗更敏感，并阻止小鼠肿瘤生长 [4]。当黑色素瘤移植到严重联合免疫缺陷小鼠体内时，双硫仑会减少其发育和血管生成；补充 Zn2+ 会放大这些效果 [4]。

[1]. Chen D, ert al. Disulfiram, a clinically used anti-alcoholism drug and copper-binding agent, induces apoptotic cell death in breast cancer cultures and?xenografts?via?inhibition?of the proteasome?activity. Cancer Res. 2006 Nov 1;66(21):10425-33.
[2]. Wang W, et al. Disulfiram-mediated inhibition of NF-kappaB activity enhances cytotoxicity of 5-fluorouracil in human colorectal cancer cell lines. Int J Cancer. 2003 Apr 20;104(4):504-11.
[3]. Cen D, et al. Disulfiram facilitates intracellular Cu uptake and induces apoptosis in human melanoma cells. J Med Chem. 2004 Dec 30;47(27):6914-20.
[4]. Brar SS, et al. Disulfiram inhibits activating transcription factor/cyclic AMP-responsive element binding protein and human melanoma growth in a metal-dependent manner in vitro, in mice and in a patient with metastatic disease. Mol Cancer Ther. 2004 Sep;3
[5]. Jun Jacob Hu, et al. Identification of pyroptosis inhibitors that target a reactive cysteine in gasdermin D. The Preprint Server For Biology, 2018,Jul. 10.
[6]. Guo F, et, al. Inhibitory effect on ovarian cancer ALDH+ stem-like cells by Disulfiram and Copper treatment through ALDH and ROS modulation. Biomed Pharmacother. 2019 Oct;118:109371

C10H20N2S4

296.54

97-77-8

S=C(SSC(N(CC)CC)=S)N(CC)CC

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.08 mg/mL (7.01 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 2.08 mg/mL (7.01 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

View More

Solubility in Formulation 3: ≥ 2.08 mg/mL (7.01 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

Solubility in Formulation 4: 30 mg/mL (101.17 mM) in Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

---

Solubility in Formulation 5: 10 mg/mL (33.72 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。