| Size | Price | Stock | Qty |
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| 250mg |
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| 500mg |
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| 1g |
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| 5g |
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| 10g |
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| 25g |
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Purity: ≥98%
Disulfiram (Disulfan; NSC 190940; Dicupral; Disetil; NSC190940; Tetraethylthiuram disulfide; TETD) is a potent and specific inhibitor of aldehyde-dehydrogenase (ALDH1) that is used for the treatment of chronic alcoholism by producing an acute sensitivity to alcohol. The mechanism of action of disulfiram is to block the metabolic processing of alcohol in the body by inhibiting acetaldehyde dehydrogenase (coverts acetaldehyde to acetic acid), thus causing unpleasant effects when even a small amount of alcohol is consumed.
| Targets |
Aldehyde-dehydrogenase (ALDH1); gasdermin D (GSDMD)
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| ln Vitro |
Disulfiram-copper complex efficiently reduces proteasome activity in cultured breast cancer MDA-MB-231 and MCF10DCIS.com cells prior to causing apoptotic cancer cell death, but not in normal immortalized MCF-10A cells [1]. A commercially utilized anti-alcoholic medication called disulfiram (DS) significantly and dose-dependently suppresses both constitutive and 5-FU-induced NF-activation. DisuLfiram has little effect on 5-FU-induced IkappaBalpha degradation, although it does reduce NF-kappaB nuclear translocation and DNA binding activity. Disulfiram synergistically increased 5-FU's cytotoxicity on both DLD-1 and RKO (WT) cell lines while also markedly enhancing 5-FU's apoptotic effect on those lines. Additionally, 5-FU chemoresistance in the 5-FU-resistant cell line H630 (5-FU) is successfully eliminated in vitro by DisuLfiram [2]. CuCl2 greatly increased DSF-induced cell death to less than 10% of the control, while oseltamivir decreased the number of viable cells [3]. At lower concentrations than disulfiram alone, disulfiram in combination with Cu2+ or Zn2+ in melanoma cells decreases cyclin A expression and inhibits in vitro proliferation [4]. The combination of DisuLfiram (0.1 nM-10 μM; 72 h) and Cu2+ increases its cytotoxicity against ovarian cancer cell lines [1].
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| ln Vivo |
Disulfiram dramatically reduced tumor development (74%) in mice containing MDA-MB-231 tumor xenografts; this was linked to proteasome inhibition and apoptosis induction [1]. In tumor tissues, ubiquitinated proteins and the natural proteasome substrates p27 and Bax accumulate, and these indicators of proteasome inhibition are used to gauge the extent of proteasome suppression. Caspases being activated and apoptotic cell nuclei forming are signs of apoptosis [1]. Disulfiram inhibits the nuclear factor-kappaB transcription factor, limits the P-glycoprotein extrusion pump, decreases angiogenesis, makes tumors more susceptible to chemotherapy, and stops tumor growth in mice [4]. When melanoma tumors are transplanted into severe combined immunodeficient mice, disulfiram reduces their development and angiogenesis; Zn2+ supplementation amplifies these effects [4].
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| Enzyme Assay |
ALDH activity was inhibited in ovarian cancer stem cells (the proportion of ALDH+ cells was reduced from 21.7% to 0.391%, 8.4% to 0%, 6.88% to 0.05% in cell lines IGROV1, SKOV3, and SKOV3IP1, respectively). DSF with or without the cofactor copper (Cu2+) exhibited cytotoxicity dose- and time-dependent and enhanced cisplatin-induced apoptosis. DSF + Cu2+ increased intracellular ROS levels triggering apoptosis of ovarian cancer stem cells (CSC). Significantly more colony and spheroid formation was observed in ALDH+ compared with ALDH- cells (P < 0.01). Moreover, ALDH+ cells were more resistant to cisplatin treatment compared with ALDH-cells (P < 0.05) and also exhibited a lower basal level of ROS. However, no significant difference in ROS accumulation nor in cellular viability was observed in ALDH + cells in comparison to ALDH- cells after pre-treatment with DSF (0.08 μM) [6].
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| Cell Assay |
The effect of disulfiram (0.15-5.0 μM) or sodium diethyldithiocarbamate (1.0 μM) on proliferation of malignant cell lines is studied in cultures stimulated with 10% FBS. Cell numbers are quantitated 24 to 72 hours later, as outlined below. In some experiments, disulfiram is added immediately after cells are plated. In other experiments, cells are plated and allowed to grow for 24 to 72 hours before fresh medium with disulfiram is added and cell numbers are assayed 24 to 72 hours later. Synergy is studied between disulfiram and N,N′-bis(2-chloroethyl-N-nitrosourea (carmustine, 1.0-1,000 μM) or cisplatin (0.1-100 μg/mL) added to medium. The effect of metal ions on disulfiram is studied with 0.2 to 10 μM Cu2+ (provided as CuSO4), Zn2+ (as ZnCl2), Ag+ (as silver lactate), or Au3+ (as HAuCl4·3H2O) ions added to growth medium, buffered to physiologic pH. To provide a biologically relevant source of copper, medium is supplemented with human ceruloplasmin at doses replicating low and high normal adult serum concentrations (250 and 500 mg/mL) [4].
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| Animal Protocol |
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| References |
[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 |
| Molecular Formula |
C10H20N2S4
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| Molecular Weight |
296.54
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| Exact Mass |
296.05093
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| Elemental Analysis |
C, 40.50; H, 6.80; N, 9.45; S, 43.25
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| CAS # |
97-77-8
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| Related CAS # |
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| Appearance |
White to yellow solid
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| LogP |
3.88
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| tPSA |
121.260
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| SMILES |
S=C(SSC(N(CC)CC)=S)N(CC)CC
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| InChi Key |
AUZONCFQVSMFAP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C10H20N2S4/c1-5-11(6-2)9(13)15-16-10(14)12(7-3)8-4/h5-8H2,1-4H3
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| Chemical Name |
Bis(diethylthiocarbamyl) disulfide
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
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. 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. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.3722 mL | 16.8611 mL | 33.7223 mL | |
| 5 mM | 0.6744 mL | 3.3722 mL | 6.7445 mL | |
| 10 mM | 0.3372 mL | 1.6861 mL | 3.3722 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04485130 | Terminated Has Results | Drug: Disulfiram Drug: Placebo |
Covid19 | University of California, San Francisco | August 18, 2021 | Phase 2 |
| NCT05626920 | Recruiting | Drug: Disulfiram 250 mg Drug: Placebo |
Inherited Retinal Dystrophy Primarily Involving Sensory Retina |
University of Washington | December 2023 | Phase 1 Phase 2 |
| NCT03891667 | Completed Has Results | Drug: Disulfiram | Fatigue Quality of Life |
Research Foundation for Mental Hygiene, Inc. |
July 31, 2019 | Phase 1 Phase 2 |
| NCT05667415 | Not yet recruiting | Drug: disulfiram and cisplatin Drug: cisplatin |
Chemotherapy；Advanced Gastric Cancer；Cisplatin；Disulfiram |
First People's Hospital of Hangzhou | August 23, 2017 | Not Applicable |
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