1、Product Data SheetDisulfiramCat. No.: HY-B0240CAS No.: 97-77-8分式: CHNS分量: 296.54作靶點(diǎn): Aldehyde Dehydrogenase (ALDH); Interleukin Related作通路: Metabolic Enzyme/Protease; Immunology/Inflammation儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 75 mg/mL (252.92 mM; Ne

2、ed ultrasonic)SolventMass1 mg 5 mg 10 mgConcentration制備儲備液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請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲存時，請?jiān)?6 個內(nèi)使，-20C 儲存時，請?jiān)?1 個內(nèi)使。體內(nèi)實(shí)驗(yàn)請根

3、據(jù)您的實(shí)驗(yàn)動物和給藥式選擇適當(dāng)?shù)娜芙獍?。以下溶解案都請先按?In Vitro 式配制澄清的儲備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的式助溶1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (8.43 mM); Clear solution此案可獲得 2.5 mg/mL (8.43 mM，飽和

4、度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (8.43 mM); Clear solution此案可獲得 2.5 mg/mL (8.43 mM，飽和度未知) 的澄清溶液。Page 1 of 2 www.MedChemE以 1 mL 作液為例，取 100

5、L 25.0 mg/mL 的澄均勻。DMSO 儲備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (8.43 mM); Clear solution此案可獲得 2.5 mg/mL (8.43 mM，飽和度未知) 的澄 溶液，此案不適于實(shí)驗(yàn)周 期在半個以上的實(shí)驗(yàn)。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 900 L 油中，混合均勻。4. 請依序添加每種溶劑： 2% DMSO 40% PEG300 5% Tween-80 5

6、3% salineSolubility: 3.43 mg/mL (11.57 mM); Suspended solution; Need ultrasonicBIOLOGICAL ACTIVITY物活性 Disulfiram (Tetraethylthiuram disulfide)特異性的醛脫氫酶1型抗體 (ALDH1) 抑制劑，可以通過對 精產(chǎn)急性敏感性來治療慢性酗 。Disulfiram 有效抑制體和細(xì)胞中脂質(zhì)體中的 GSDMD 孔形成，炎性體介導(dǎo)的細(xì)胞凋亡和IL-1 分泌。IC & Target IL-1體外研究 Disulfiram-copper complex potently i

7、nhibits the proteasomal activity in cultured breast cancer MDA-MB-231 andMCF10DCIS.com cells, but not normal, immortalized MCF-10A cells, before induction of apoptotic cancer cell death1.Disulfiram (DS), a clinically used anti-alcoholism drug, strongly inhibits constitutive and 5-FU-induced NF-kappa

8、Bactivity in a dose-dependent manner. Disulfiram inhibits both NF-kappaB nuclear translocation and DNA bindingactivity but has no effect on 5-FU-induced IkappaBalpha degradation. Disulfiram significantly enhances the apoptoticeffect of 5-FU on DLD-1 and RKO(WT) cell lines and synergistically potenti

9、ated the cytotoxicity of 5-FU to both celllines. Disulfiram also effectively abolishes 5-FU chemoresistance in a 5-FU resistant cell line H630(5-FU) in vitro2. Oseltamivir decreases the number of viable cells, and the addition of CuCl2 significantly enhances the DSF-inducedcell death to less than 10

10、% of control3. 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 alone4.體內(nèi)研究 Disulfiram significantly inhibits the tumor growth (by 74%), associated with in vivo proteasome in

11、hibition (asmeasured by decreased levels of tumor tissue proteasome activity and accumulation of ubiquitinated proteins andnatural proteasome substrates p27 and Bax) and apoptosis induction (as shown by caspase activation and apoptoticnuclei formation) in mice bearing MDA-MB-231 tumor xenografts1. D

12、isulfiram blocks the P-glycoprotein extrusionpump, inhibits the transcription factor nuclear factor-kappaB, sensitizes tumors to chemotherapy, reducesangiogenesis, and inhibits tumor growth in mice. Disulfiram inhibits growth and angiogenesis in melanomastransplanted in severe combined immunodeficie

13、nt mice, and these effects are potentiated 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 malignant celllines is studied in cultures stimulated with 10% FBS. Cell numbers are quantitated 24 to 72 hours

14、 later, as outlinedbelow. In some experiments, disulfiram is added immediately after cells are plated. In other experiments, cells areplated and allowed to grow for 24 to 72 hours before fresh medium with disulfiram is added and cell numbers areassayed 24 to 72 hours later. Synergy is studied betwee

15、n 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 isstudied with 0.2 to 10 M Cu2+ (provided as CuSO4), Zn2+ (as ZnCl2), Ag+ (as silver lactate), or Au3+ (as HAuCl43H2O) ions added to growt

16、h medium, buffered to physiologic pH. To provide a biologically relevant source of copper,Page 2 of 3 www.MedChemEmedium is supplemented with human ceruloplasmin at doses replicating low and high normal adult serumconcentrations (250 and 500 mg/mL).MCE has not independently confirmed the accuracy of

17、 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 either aAdministration 4 standard diet containing 87 ppm zinc or a zinc-supplemented diet containing 1,000 ppm Zn2+ as zinc acetate. Miceare injecte

18、d s.c. in the right groin with 5106 cells from a highly aggressive malignant melanoma obtained from aCarolinas Medical Center patient. The frozen tumor is passaged twice in SCID mice to adapt it to in vivo growthbefore use in these experiments. On the day of tumor injection, all mice began daily adm

19、inistration of drug. Drug isgiven in a total volume of 0.2 mL by gastric gavage via smooth Teflon-tipped needles inserted transorally into thestomach. Four groups are studied: tumor control (n=10; 0.2 mL olive oil daily; zinc diet of 87 ppm); zinc-supplemented control (n=10; 0.2 mL olive oil daily;

20、zinc diet of 1,000 ppm); disulfiram (n=10; 200 mg/kg/d disulfiramin 0.2 mL olive oil; zinc diet of 87 ppm); and zinc-supplemented diet + disulfiram (n=10; 200 mg/kg/d disulfiram in0.2 mL olive oil; zinc diet of 1,000 ppm). Mice are examined daily, the tumor is measured in two dimensions, and thetumo

21、r volume is estimated using the formula for an elipse. When estimated tumor volume approached 500 mm3within any animal, all mice are euthanized. Tumors are excised, weighed, fixed in formalin, sectioned, and stained orimmunostained for factor VIII. Slides are coded and examined by a blinded observer

22、 who identified vessels asdeposits of red cells. For each slide, the number of vessels is counted in four different fields representative of thetumor. The average number of vessels per field is averaged per biopsy specimen and used to evaluate tumorvascularity.MCE has not independently confirmed the

23、 accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) J Exp Med. 2019 Nov 4;216(11):2562-2581. Environ Int. 2019 Jun;127:694-703. Cancer Manag Res. 2019; 11: 38873898. bioRxiv. 2020 Mar. Nature Cancer. 2020 Jan.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFEREN

24、CES1. Chen D, ert al. Disulfiram, a clinically used anti-alcoholism drug and copper-binding agent, induces apoptotic cell death in breast cancer culturesand?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 JCancer. 2003 Apr 20;104(4):504-11.3. Cen