Disulfiram-Tetraethylthiuram-disulfide-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEDisulfiramCat. No.: HY-B0240CAS No.: 97-77-8Synonyms: Tetraethylthiuram disulfide; TETD分式: CHNS分量: 296.54作靶点: Aldehyde Dehydrogenase (ALDH)作通路: Metabolic Enzyme/Protease储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-

2、20C 1 month溶解性数据体外实验 DMSO : 75 mg/mL (252.92 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 3.3722 mL 16.8611 mL 33.7223 mL5 mM 0.6744 mL 3.3722 mL 6.7445 mL10 mM 0.3372 mL 1.6861 mL 3.3722 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，

3、再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (8.43 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (8.43 mM); Clear solution3. 请依序添加每种溶剂：

4、10% DMSO 90% corn oil1/3 Master of Small Molecules 您边的抑制剂师www.MedChemESolubility: 2.5 mg/mL (8.43 mM); Clear solution4. 请依序添加每种溶剂： 2% DMSO 40% PEG300 5% Tween-80 53% salineSolubility: 3.43 mg/mL (11.57 mM); Suspended solution; Need ultrasonicBIOLOGICAL ACTIVITY物活性 Disulfiram特异性的醛脱氢酶1型抗体 (ALDH1) 抑制剂，

5、可以通过对 精产急性敏感性来治疗慢性酗酒。体外研究 Disulfiram-copper complex potently inhibits the proteasomal activity in cultured breast cancer MDA-MB-231and MCF10DCIS.com cells, but not normal, immortalized MCF-10A cells, before induction of apoptoticcancer cell death 1. Disulfiram (DS), a clinically used anti-alcoholism

6、 drug, strongly inhibits constitutive and5-FU-induced NF-kappaB activity in a dose-dependent manner. Disulfiram inhibits both NF-kappaB nucleartranslocation and DNA binding activity but has no effect on 5-FU-induced IkappaBalpha degradation.Disulfiram significantly enhances the apoptotic effect of 5

7、-FU on DLD-1 and RKO(WT) cell lines andsynergistically potentiated the cytotoxicity of 5-FU to both cell lines. Disulfiram also effectively abolishes 5-FUchemoresistance in a 5-FU resistant cell line H630(5-FU) in vitro 2. Oseltamivir decreases the number ofviable cells, and the addition of CuCl2 si

8、gnificantly enhances the DSF-induced cell death to less than 10% ofcontrol 3. Disulfiram given to melanoma cells in combination with Cu2+ or Zn2+ decreases expression ofcyclin A and reduces proliferation in vitro at lower concentrations than disulfiram alone 4.体内研究 Disulfiram significantly inhibits

9、the tumor growth (by 74%), associated with in vivo proteasome inhibition (asmeasured by decreased levels of tumor tissue proteasome activity and accumulation of ubiquitinated proteinsand natural proteasome substrates p27 and Bax) and apoptosis induction (as shown by caspase activationand apoptotic n

10、uclei 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 tochemotherapy, reduces angiogenesis, and inhibits tumor growth in mice. Disulfiram inhibits growth andangio

11、genesis in melanomas transplanted in severe combined immunodeficient mice, and these effects arepotentiated by Zn2+ supplementation 4.PROTOCOLCell Assay 4 The effect of disulfiram (0.15-5.0 M) or sodium diethyldithiocarbamate (1.0 M) on proliferation of malignantcell lines is studied in cultures sti

12、mulated 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 otherexperiments, cells are plated and allowed to grow for 24 to 72 hours before fresh medium with disulfiram isadded and cell nu

13、mbers 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 M) or cisplatin (0.1-100 g/mL) added to medium.The effect of metal ions on disulfiram is studied with 0.2 to 10 M Cu2+ (provided as CuSO4), Zn2+ (asZnCl2), Ag+

14、 (as silver lactate), or Au3+ (as HAuCl43H2O) ions added to growth medium, buffered tophysiologic pH. To provide a biologically relevant source of copper, medium is supplemented with humanceruloplasmin at doses replicating low and high normal adult serum concentrations (250 and 500 mg/mL).2/3 Master

15、 of Small Molecules 您边的抑制剂师www.MedChemEMCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Adult female CB17-SCID mice are housed in a protected laminar flow facility with access to water and eitherAdministration 4 a standard diet containing 87 ppm z

16、inc or a zinc-supplemented diet containing 1,000 ppm Zn2+ as zincacetate. Mice are injected s.c. in the right groin with 5106 cells from a highly aggressive malignantmelanoma obtained from a Carolinas Medical Center patient. The frozen tumor is passaged twice in SCIDmice to adapt it to in vivo growt

17、h before use in these experiments. On the day of tumor injection, all micebegan daily administration of drug. Drug is given in a total volume of 0.2 mL by gastric gavage via smoothTeflon-tipped needles inserted transorally into the stomach. Four groups are studied: tumor control (n=10; 0.2mL olive o

18、il daily; zinc diet of 87 ppm); zinc-supplemented control (n=10; 0.2 mL olive oil daily; zinc diet of1,000 ppm); disulfiram (n=10; 200 mg/kg/d disulfiram in 0.2 mL olive oil; zinc diet of 87 ppm); and zinc-supplemented diet + disulfiram (n=10; 200 mg/kg/d disulfiram in 0.2 mL olive oil; zinc diet of

19、 1,000 ppm).Mice are examined daily, the tumor is measured in two dimensions, and the tumor volume is estimated usingthe formula for an elipse. When estimated tumor volume approached 500 mm3 within any animal, all miceare euthanized. Tumors are excised, weighed, fixed in formalin, sectioned, and sta

20、ined or immunostained forfactor VIII. Slides are coded and examined by a blinded observer who identified vessels as deposits of redcells. For each slide, the number of vessels is counted in four different fields representative of the tumor. Theaverage number of vessels per field is averaged per biop

21、sy specimen and used to evaluate tumorvascularity.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Environ Int. 2019 Jun;127:694-703. Cancer Manag Res. 2019; 11: 38873898. bioRxiv. 2019 Aug. Patent. US20180263995A1.See more customer validatio

22、ns on HYPERLINK / www.MedChemEREFERENCES1. Chen D, ert al. Disulfiram, a clinically used anti-alcoholism drug and copper-binding agent, induces apoptotic cell death in breast cancercultures 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 activi