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    InvivoChem Cat #: V0859
    CAS #: 97-77-8Purity ≥98%

    Description: 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.  

    References: Cancer Res. 2006 Nov 1;66(21):10425-33; J Med Chem. 2004 Dec 30;47(27):6914-20; Mol Cancer Ther. 2004 Sep;3(9):1049-60.

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    Molecular Weight (MW)296.54
    CAS No.97-77-8
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 59 mg/mL (199.0 mM)
    Water: <1 mg/mL
    Ethanol: 59 mg/mL (199.0 mM)
    SynonymsDisulfan; NSC 190940; Dicupral; Disetil; NSC190940; NSC-190940; Disulfiram; 

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    In Vitro

    In vitro activity: Disulfiram-copper complex potently inhibits the proteasomal activity in cultured breast cancer MDA-MB-231 and cells, but not normal, immortalized MCF-10A cells, before induction of apoptotic cancer cell death. 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. 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. Disulfiram given to melanoma cells in combination with Cu2+ or Zn2+ decreases expression of cyclin A and reduces proliferation in vitro at lower concentrations than disulfiram alone.

    Kinase Assay:  The chymotrypsin-like activity of purified 20S proteasome was measured. Briefly, 17.5 ng of purified 20S proteasome were incubated in 100 μL of assay buffer (50 mmol/L Tris-HCl, pH 7.5) with or without different concentrations of copper chloride, Disulfiram, or the Disulfiram-copper mixture and 10 μmol/L fluorogenic peptide substrate Suc-LLVY-AMC (for the proteasomal chymotrypsin-like activity) for 2 hrs at 37℃. After incubation, production of hydrolyzed AMC groups was measured with a Wallac Victor3 multilabel counter with an excitation filter of 365 nm and an emission filter of 460 nm.

    Cell Assay: The Disulfiram-copper complex potently inhibited the proteasomal activity in cultured breast cancer MDA-MB-231 cells, before induction of apoptotic cancer cell death.

    In VivoDisulfiram 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. 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 Zn2+ supplementation.
    Animal modelMice bearing MDA-MB-231 tumor xenografts 
    Formulation & Dosage50 mg/kg/d; p.o.; for 29 days 

    Cancer Res. 2006 Nov 1;66(21):10425-33; J Med Chem. 2004 Dec 30;47(27):6914-20; Mol Cancer Ther. 2004 Sep;3(9):1049-60.

    These protocols are for reference only. InvivoChem does not independently validate these methods.


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