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Disulfiram

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Chemical Structure| 97-77-8 同义名 : 双硫仑;双硫伦;二硫化四乙基秋兰姆 ;Tetraethylthiuram disulfide;TETD;Disulfan;Disetil;Dicupral;NSC 25953;NSC 190940
CAS号 : 97-77-8
货号 : A912727
分子式 : C10H20N2S4
纯度 : 98%+
分子量 : 296.539
MDL号 : MFCD00009048
存储条件：

粉末 Sealed in dry,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 80 mg/mL(269.78 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

2% DMSO+30% PEG 300+5% Tween 80+water 2.5 mg/mL

生物活性
靶点

  • Dehydrogenase
描述 Aldehyde dehydrogenase can catalyze the oxidation of aldehydes by converting them to carboxylic acids, which leave the liver and are metabolized by the body's muscle and heart. Thus the accumulation of aldehydes do harm to human. Disulfiram (DSF) is currently a clinical used inhibitor for aldehyde dehydrogenase treating alcoholism with average IC50 value of 300 nM. Moreover, studies showed that DSF may also have antitumor and chemosensitizing activities. DSF treatment could inhibit growth of TNBC cells by increasing cell death and senescence and induced 38% cell death after 72 hrs treatment combined with doxorubicin. Besides, DSF also caused many MDA-MB-231 cells death and enlarged cell morphology, showing 23% X-gal-positive cells. Cancer stem cells (CSCs) in TNBC cell lines were inhibited by 5% with DSF treatment alone or by 65% with combined treatment with doxorubicin.[1] In purified rabbit 20S proteasome assay, DSF-copper complex inhibited the chymotrypsin-like activity with an IC50 value of 7.5 μM while DSF alone had no effect even at concentration of 20 μM. The complex also led to 95% reduction of the proteasomal chymotrypsin-like activity in the breast cancer cells and inhibited proliferation of MDA-MB-231 cells by 55%, 65% and 85% when the concentrations were 5, 10, 20 μM respectively. Besides, the complex induced apoptotic cell death due to the detection of PARP cleavage in the breast cancer cells, suggesting that the copper ion should be responsible for the inhibiting ability of DSF. Treated the MCF-10A (normal cells) and MCF10DCIS.com cell lines (malignant cells) with 20 μM the complex led to 97% reduction of proteasomal chymotrypsin-like activity in MCF10DCIS.com cell lines but no effect on the MCF-10A cell lines, suggesting the nontoxic effect of the DSF-copper complex in normal cells. The CuCl2-precultured MDA-MB-231 cells treated with 20 μM DSF also showed 67% inhibition of the proteasomal activity as well as the accumulation of PARP cleavage, suggesting copper ion is important for DSF treatment. Furthermore, DSF-treated tumors resulted in 74% inhibition of tumor growth and 87% inhibition of the proteasomal activity[2] . Disulfiram potently inhibited GSDMD pore formation in liposomes and inflammasome-mediated pyroptosis and IL-1β secretion in human and mouse cells. It covalently modify a conserved Cys (Cys191 in human and Cys192 in mouse GSDMD) that is critical for pore formation[3]. It also works as a pyroptosis inhibitor by blocking gasdermin D pore formation[4].
作用机制 Disulfiram is capable of binding copper react with sulfhydryl groups.[2]
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
CHO cells Function assay Agonist activity at human TRPA1 channel expressed in CHO cells assessed as increase in intracellular calcium levels, EC50=3 μM 20356305
human MCF10A cells Proliferation assay 72 h Antiproliferative activity against human MCF10A cells after 72 hrs by MTT assay, IC50=10 μM 20222671
human MDA-MB-231 cells Proliferation assay 72 h Antiproliferative activity against human MDA-MB-231 cells expressing BCA2 and ERalpha after 72 hrs by MTT assay, IC50=0.32 μM 20222671
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT00372749 Alcoholic Intoxication, Chroni... 展开 >>c 收起 << Not Applicable Completed - France ... 展开 >> Hopital Emile Roux APHP Limeil-Brevannes, France, 94450 收起 <<
NCT02309801 Healthy Phase 1 Completed - Spain ... 展开 >> Parc de Salut Mar. Barcelona, Spain, 08003 收起 <<
NCT02770378 Glioblastoma Phase 1 Active, not recruiting March 2020 Germany ... 展开 >> University of Ulm School of Medicine Ulm, Baden-Württemberg, Germany, 89081 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.37mL

0.67mL

0.34mL

16.86mL

3.37mL

1.69mL

33.72mL

6.74mL

3.37mL
参考文献

[1]Robinson TJ, Pai M, et al. High-throughput screen identifies disulfiram as a potential therapeutic for triple-negative breast cancer cells: interaction with IQ motif-containing factors. Cell Cycle. 2013;12(18):3013-24.

[2]Chen D, Cui QC, et 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;66(21):10425-33.

[3]Identification of pyroptosis inhibitors that target a reactive cysteine in gasdermin D

[4]Hu JJ, Liu X, Xia S, Zhang Z, Zhang Y, Zhao J, Ruan J, Luo X, Lou X, Bai Y, Wang J, Hollingsworth LR, Magupalli VG, Zhao L, Luo HR, Kim J, Lieberman J, Wu H. FDA-approved disulfiram inhibits pyroptosis by blocking gasdermin D pore formation. Nat Immunol. 2020 Jul;21(7):736-745. doi: 10.1038/s41590-020-0669-6. Epub 2020 May 4. PMID: 32367036; PMCID: PMC7316630.

[5]Karamanakos PN, Pappas P, et al. Differentiation of disulfiram effects on central catecholamines and hepatic ethanol metabolism. Pharmacol Toxicol. 2001 Feb;88(2):106-10.

[6]Fossa AA, Carlson GP, et al. Antiarrhythmic effect of disulfiram in various cardiotoxic models. Pharmacology. 1983;26(3):164-71.