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Catalog: | HY-B0240 |
Brand: | MCE |
CAS: | 97-77-8 |
MDL | MFCD00009048 |
---|---|
Molecular Weight | 296.54 |
Molecular Formula | C10H20N2S4 |
SMILES | S=C(SSC(N(CC)CC)=S)N(CC)CC |
Disulfiram (Tetraethylthiuram disulfide) is a specific inhibitor of aldehyde-dehydrogenase (ALDH1) , used for the treatment of chronic alcoholism by producing an acute sensitivity to alcohol. Disulfiram inhibits gasdermin D (GSDMD) pore formation in liposomes and inflammasome-mediated pyroptosis and IL-1β secretion in human and mouse cells. Disulfiram + Cu 2+ increases intracellular ROS levels triggering apoptosis of ovarian cancer stem cells [1-6] .
IL-1
|
IL-1β
|
Disulfiram-copper complex potently inhibits the proteasomal activity in cultured breast cancer MDA-MB-231 and MCF10DCIS.com cells, but not normal, immortalized MCF-10A cells, before induction of apoptotic cancer cell death
[1]
. Disulfiram (DS), a clinically used anti-alcoholism drug, strongly inhibits constitutive and 5-FU-induced NF-kappaB activity in a dose-dependent manner. Disulfiram inhibits both NF-kappaB nuclear translocation and DNA binding activity but has no effect on 5-FU-induced IkappaBalpha degradation. Disulfiram significantly enhances the apoptotic effect of 5-FU on DLD-1 and RKO(WT) cell lines and synergistically potentiated the cytotoxicity of 5-FU to both cell lines. Disulfiram also effectively abolishes 5-FU chemoresistance in a 5-FU resistant cell line H630(5-FU) in vitro
[2]
. Oseltamivir decreases the number of viable cells, and the addition of CuCl
2
significantly enhances the DSF-induced cell death to less than 10% of control
[3]
. Disulfiram given to melanoma cells in combination with Cu
2+
or Zn
2+
decreases expression of cyclin A and reduces proliferation in vitro at lower concentrations than disulfiram alone
[4]
.
Disulfiram (0.1 nM-10 μM; 72 h) + Cu
2+
combination enhances the cytotoxicity on ovarian cancer cell lines
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Disulfiram significantly inhibits the tumor growth (by 74%), associated with in vivo proteasome inhibition (as measured by decreased levels of tumor tissue proteasome activity and accumulation of ubiquitinated proteins and natural proteasome substrates p27 and Bax) and apoptosis induction (as shown by caspase activation and apoptotic nuclei formation) in mice bearing MDA-MB-231 tumor xenografts [1] . Disulfiram blocks the P-glycoprotein extrusion pump, inhibits the transcription factor nuclear factor-kappaB, sensitizes tumors to chemotherapy, reduces angiogenesis, and inhibits tumor growth in mice. Disulfiram inhibits growth and angiogenesis in melanomas transplanted in severe combined immunodeficient mice, and these effects are potentiated by Zn 2+ supplementation [4] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
NCT Number | Sponsor | Condition | Start Date | Phase |
---|---|---|---|---|
NCT00913484 | Yale University|National Institute on Drug Abuse (NIDA) |
Cocaine Dependence|Opioid Dependency
|
October 2000 | Phase 2 |
NCT00431262 | Psykiatrisk Center Gentofte |
Alcoholism
|
February 2007 | Phase 4 |
NCT02671890 | Mayo Clinic|National Cancer Institute (NCI) |
Metastatic Pancreatic Adenocarcinoma|Refractory Malignant Solid Neoplasm|Stage IV Pancreatic Cancer AJCC v8
|
February 25, 2016 | Phase 1 |
NCT00218608 | University of Arkansas|Yale University |
Cocaine-Related Disorders|Opioid-Related Disorders
|
April 2001 | Phase 2 |
NCT01777919 | Olympion Medical Center|University of Ioannina|University of Eastern Finland|University of Ulm |
Glioblastoma Multiforme
|
January 2017 | Phase 2 |
NCT02134002 | Assistance Publique - Hôpitaux de Paris|National Research Agency, France |
Cocaine Dependence
|
June 2014 | Phase 4 |
NCT03891667 | Research Foundation for Mental Hygiene, Inc.|FDC Foundation |
Fatigue|Quality of Life
|
July 31, 2019 | Phase 1|Phase 2 |
NCT00149630 | Baylor College of Medicine|National Institute on Drug Abuse (NIDA)|Yale University |
Cocaine Dependence|Opioid Dependence
|
January 2005 | Phase 2 |
NCT02678975 | Sahlgrenska University Hospital, Sweden|St. Olavs Hospital|Lund University Hospital|Karolinska University Hospital|University Hospital, Linkoeping|Region Örebro County|Ryhov County Hospital|Uppsala University Hospital |
Glioma|Glioblastoma
|
January 2017 | Phase 2|Phase 3 |
NCT04521335 | University of Utah|Cantex Pharmaceuticals |
Multiple Myeloma
|
May 21, 2021 | Phase 1 |
NCT03323346 | The Institute of Molecular and Translational Medicine, Czech Republic|University Hospital Olomouc |
Breast Neoplasm Female|Metastatic Breast Cancer
|
September 29, 2017 | Phase 2 |
NCT01286259 | University of California, San Francisco|Johns Hopkins University |
HIV-1 Infection
|
January 2011 | Not Applicable |
NCT00731133 | University of Arkansas |
Methamphetamine Dependence
|
August 2008 | Phase 1|Phase 2 |
NCT00721526 | University of New Mexico|National Institute on Alcohol Abuse and Alcoholism (NIAAA) |
Alcohol Dependence|Anxiety Disorder
|
August 2009 | Phase 4 |
NCT02715609 | Washington University School of Medicine |
Glioblastoma Multiforme
|
June 15, 2016 | Phase 1|Phase 2 |
NCT05162001 | Universidad de Guanajuato|Laboratorios Doctor Macías |
Obesity; Drug
|
November 21, 2021 | Early Phase 1 |
NCT04594343 | ETICA|Spring Research Foundation |
Covid19
|
November 20, 2020 | Phase 2 |
NCT00142844 | University of Pennsylvania|National Institute on Drug Abuse (NIDA) |
Alcohol-Related Disorders|Alcoholism|Cocaine-Related Disorders
|
September 1999 | Phase 2 |
NCT00395850 | University of Arkansas|National Institute on Drug Abuse (NIDA) |
Cocaine Dependence
|
April 2007 | Phase 2 |
NCT00571116 | University of California, Irvine |
Metastatic Melanoma
|
September 2006 | Phase 1 |
NCT05210374 | Case Comprehensive Cancer Center |
Relapsed Sarcomas
|
December 2022 | Phase 1 |
NCT02770378 | University of Ulm|Reliable Cancer Therapies|Anticancer Fund, Belgium |
Glioblastoma
|
November 2016 | Phase 1|Phase 2 |
NCT01907165 | Washington University School of Medicine |
Glioblastoma
|
October 10, 2013 | Early Phase 1 |
NCT04485130 | University of California, San Francisco |
Covid19
|
May 1, 2021 | Phase 2 |
NCT02735577 | New York State Psychiatric Institute |
Alcohol Use Disorder
|
March 2016 | Phase 4 |
NCT00435435 | Finnish Institute for Health and Welfare |
Alcohol Dependence
|
September 2000 | Phase 4 |
NCT01118741 | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins |
Prostate Cancer
|
May 2010 | Not Applicable |
NCT00000278 | Yale University|National Institute on Drug Abuse (NIDA)|VA Connecticut Healthcare System |
Alcohol-Related Disorders|Cocaine-Related Disorders
|
September 1994 | Phase 2 |
NCT04265274 | National Cancer Institute, Slovakia |
Metastatic Breast Cancer
|
January 1, 2020 | Phase 2 |
NCT04502589 | Virginia Commonwealth University|National Institute on Alcohol Abuse and Alcoholism (NIAAA) |
Alcohol Disorders
|
October 15, 2020 | Phase 1|Phase 2 |
NCT03151772 | Sahlgrenska University Hospital, Sweden |
Glioblastoma
|
January 29, 2018 | Early Phase 1 |
NCT00256230 | John P. Fruehauf|University of California, Irvine |
Stage IV Melanoma
|
January 2002 | Phase 1|Phase 2 |
NCT02963051 | Daniel George, MD|Give 1 For Dad Campaign|The V Foundation for Cancer Research|Peter Michael Foundation|Cantex Pharmaceuticals|Duke University |
Prostate Cancer
|
July 11, 2017 | Phase 1 |
NCT02101008 | University of Utah |
Melanoma
|
March 2010 | Phase 2 |
NCT04287790 | Yale University |
Alcohol Use Disorder
|
January 1, 2020 | |
NCT03212599 | Johannes Gutenberg University Mainz |
Alcohol Addiction
|
May 2013 | |
NCT00350870 | Yale University|National Institute on Drug Abuse (NIDA) |
Cocaine Abuse
|
April 2005 | Phase 1 |
NCT01944371 | University of California, San Francisco|Monash University|amfAR, The Foundation for AIDS Research|National Institute of Allergy and Infectious Diseases (NIAID) |
HIV|Human Immunodeficiency Virus
|
September 2013 | Phase 1|Phase 2 |
NCT00580827 | Yale University|National Institute on Drug Abuse (NIDA) |
Cocaine-Related Disorder|Opiate Dependence
|
September 2003 | Not Applicable |
NCT00002065 | St. Vincent´s Medical Center|NIH AIDS Clinical Trials Information Service |
HIV Infections
|
Not Applicable | |
NCT00094289 | National Institute on Drug Abuse (NIDA) |
Alcohol-Related Disorders|Cocaine-Related Disorders
|
August 2004 | Phase 1 |
NCT00878306 | University of California, San Francisco|National Institute on Drug Abuse (NIDA) |
HIV Infections|Drug Abuse
|
November 2008 | Phase 1 |
NCT03363659 | Aurora Health Care |
Glioblastoma|Glioblastoma Multiforme
|
March 28, 2018 | Phase 2 |
NCT03950830 | National Cancer Institute, Slovakia |
Germ Cell Tumor
|
May 14, 2019 | Phase 2 |
NCT00742911 | University of Utah |
Cancer
|
July 2008 | Phase 1 |
NCT00312819 | Hadassah Medical Organization|Augusta Hospital, Berlin |
Non-small Cell Lung Cancer
|
March 2006 | Phase 2|Phase 3 |
NCT00729300 | National Institute on Drug Abuse (NIDA) |
Cocaine Addiction
|
April 2006 | Phase 1|Phase 2 |
Solid
Room temperature in continental US; may vary elsewhere.
Powder | -20°C | 3 years |
---|---|---|
4°C | 2 years | |
In solvent | -80°C | 6 months |
-20°C | 1 month |
DMSO : 75 mg/mL ( 252.92 mM ; Need ultrasonic)
Concentration Solvent Mass | 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 |
Add each solvent one by one: corn oil
Solubility: 30 mg/mL (101.17 mM); Clear solution; Need ultrasonic
Add each solvent one by one: 50% PEG300 >> 50% saline
Solubility: 10 mg/mL (33.72 mM); Suspended solution; Need ultrasonic
Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline)
Solubility: ≥ 2.08 mg/mL (7.01 mM); Clear solution
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.08 mg/mL (7.01 mM); Clear solution
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