葡萄糖酸铜/双硫仑(Copper Gluconate/Disulfiram) - 药物靶点：ADHs_在研适应症：乳腺癌，胶质母细胞瘤，多形性胶质母细胞瘤_专利_临床

概要

基本信息

药物类型

小分子化药

别名

DSF-Cu、Dicopp、Disulfiram/copper gluconate

+ [2]

靶点

ADHs

作用方式

抑制剂

作用机制

ADHs抑制剂(乙醇脱氢酶家族抑制剂)

治疗领域

肿瘤神经系统疾病皮肤和肌肉骨骼疾病+ [1]

在研适应症

乳腺癌胶质母细胞瘤多形性胶质母细胞瘤

非在研适应症

肝癌转移性胰腺癌复发性胶质母细胞瘤+ [1]

原研机构

CANTEX, Inc.

在研机构

Washington University School of Medicine

CANTEX, Inc.

非在研机构

Cantex Pharmaceuticals, Inc.

University of Utah

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

分子式C12H22CuO14

InChIKeyOCUCCJIRFHNWBP-IYEMJOQQSA-L

CAS号527-09-3

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关联

9

项与葡萄糖酸铜/双硫仑相关的临床试验

NCT05210374

/ Recruiting临床1期IIT

Disulfiram With Copper Gluconate and Liposomal Doxorubicin in Patients With Treatment-Refractory Sarcomas

The purpose of this study is to test the safety of combining the disulfiram (DSF) and copper gluconate (Cu) to liposomal doxorubicin to treat patients with sarcomas that recurred or did not respond to initial treatment.

开始日期2023-03-09

申办/合作机构

The Case Comprehensive Cancer Center

NCT04521335

/ Terminated临床1期IIT

A Phase I Study of Disulfiram and Copper Gluconate in Patients With Treatment-Refractory Multiple Myeloma

This is a phase I, open-label trial of disulfiram in combination with copper gluconate in patients with treatment-refractory multiple myeloma. The trial is designed to assess the Phase 2 Recommended Dose (RP2D) of disulfiram and copper gluconate in combination. The trial will open with dose escalation, followed to an expansion cohort to further characterize the safety and tolerance of the combination.
Dose escalation will utilize a standard 3+3 design and will test up to five dose levels. Dose levels will be separated into two sequential parts defined by the fixed dose of copper as copper gluconate administered with ascending doses of disulfiram. Part 1 of dose escalation will consist of dose levels 0 and 1 with the option to reduce to Dose Level -1 if Dose Level 0 is deemed intolerable. Part 2 will test dose levels 2 and 3. The Dose Level deemed to be the RP2D will be used in dose expansion.

开始日期2021-05-21

申办/合作机构

University of Utah

[+1]

NCT03714555

/ Terminated临床2期IIT

A Phase II Pilot Study of Disulfiram and Copper Gluconate in Patients With Metastatic Pancreatic Cancer and Rising CA-19-9 Levels While Receiving Abraxane-Gemcitabine or FOLFIRINOX or Single-Agent Gemcitabine

This is an open-label Phase 2 Pilot study to evaluate Disulfiram + Copper Gluconate in patients metastatic pancreatic cancer whose CA-19-9 levels rise while receiving nab-paclitaxel (Abraxane) plus gemcitabine (Gemzar) or FOLFIRINOX or single-agent gemcitabine (Gemzar). Patient must have received a minimum of 8 weeks of treatment and have rising CA-19-9 levels in the absence of radiographic evidence of progression.

开始日期2019-10-17

申办/合作机构

Scottsdale Healthcare Corp.

[+1]

100 项与葡萄糖酸铜/双硫仑相关的临床结果

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100 项与葡萄糖酸铜/双硫仑相关的转化医学

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100 项与葡萄糖酸铜/双硫仑相关的专利（医药）

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36

项与葡萄糖酸铜/双硫仑相关的文献（医药）

2024-12-01·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

Disulfiram/copper complex improves the effectiveness of the WEE1 inhibitor Adavosertib in p53 deficient non-small cell lung cancer via ferroptosis

Article

作者: Su, Bo ; Liu, Di ; Xu, Yaping ; Shi, Minxing ; Tai, Qidong ; Yao, Xiaojuan ; Dai, Mengyuan ; Ding, Xi ; Fei, Ke ; Cao, Jingxue ; Xu, Wen

Cancer cells lacking functional p53 exhibit poor prognosis, necessitating effective treatment strategies. Inhibiting WEE1, the G2/M cell cycle checkpoint gatekeeper, represents a promising approach for treating p53-deficient NSCLC. Here, we investigate the connection between p53 and WEE1, as well as explore a synergistic therapeutic approach for managing p53-deficient NSCLC. Our study reveals that p53 deficiency upregulates both protein levels and kinase activity of WEE1 by inhibiting its SUMOylation process, thereby enhancing the susceptibility of p53-deficient NSCLC to WEE1 inhibitors. Furthermore, we demonstrate that the WEE1 inhibitor Adavosertib induces intracellular lipid peroxidation, specifically in p53-deficient NSCLC cells, suggesting potential synergy with pro-oxidant reagents. Repurposing Disulfiram (DSF), an alcoholism medication used in combination with copper (Cu), exhibits pro-oxidant properties against NSCLC. The levels of WEE1 protein in p53-deficient NSCLC cells treated with DSF-Cu exhibit a time-dependent increase. Subsequent evaluation of the combination therapy involving Adavosertib and DSF-Cu reveals reduced cell viability along with smaller tumor volumes and lighter tumor weights observed in both p53-deficient cells and xenograft models while correlating with solute carrier family 7-member 11 (SLC7A11)/glutathione-regulated ferroptosis pathway activation. In conclusion, our findings elucidate the molecular interplay between p53 and WEE1 and unveil a novel synergistic therapeutic strategy for treating p53-deficient NSCLC.

2024-09-25·Current Cancer Drug Targets

Disulfiram-Copper Potentiates Anticancer Efficacy of Standard Chemo-therapy Drugs in Bladder Cancer Animal Model through ROS-Autophagy-Ferroptosis Signalling Cascade

Article

作者: Panwar, Ritika ; Rastogi, Pulkit ; Kakkar, Ashish ; Konar, Monidipa ; Kumar, Sandeep ; Singh, Sheetal ; Mavuduru, Ravimohan S. ; Dey, Sumit ; Sharma, Neeru ; Naithani, Priyanka ; Pattanaik, Smita

Background:Cost-effective management of Urinary Bladder Cancer (UBC) is an unmet needAims:Our study aims to demonstrate the efficacy of a drug repurposing strategy by using disulfiram (DSF) and copper gluconate (Cu) as an add-on treatment combination to traditional GC-based chemother-apy against N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced UBC mice (C57J) model.Methods:Male C57BL/6J mice were given 0.05% BBN in drinking water ad libitum, and tumour for-mation was verified by histological and physical evaluation. Animals were subsequently divided into eight groups and received treatment with different drug combinations. Control animals received only ve-hicle (DMSO). At the end of the treatment schedule, the bladder tumour was excised and further used to check the expression (mRNA and protein) of ALDH1 isoenzymes using qRT-PCR, western blot, and IHC methods. Autophagy induction was assessed by quantifying the expression of LC3B and SQSTM1/p62 proteins through IHC. Biochemical analysis of superoxide dismutase (SOD), reduced glutathione (GSH), and lipid peroxidation levels in the freshly isolated tumours was performed to check the alterations in the antioxidant system caused by combination treatment.Results:We observed significant induction of an invasive form of bladder cancer in the mice after nine-teen weeks of BBN exposure. The animals began exhibiting early indications of inflammatory alterations as early as the sixth week following BBN treatment. Furthermore, the wet bladder weight and overall tu-mour burden were significantly decreased (p< 0.0001) by DSF-Cu co-treatment in addition to the GC-based chemotherapy. Real-time PCR analysis revealed that treatment with disulfiram and copper glu-conate significantly decreased (p<0.0001) the mRNA expression of ALDH1 isoenzymes. Comparing the triple drug combination group (GC+DSF-Cu) to the untreated mice, a significant rise in LC3B puncta (p<0.0001) and a decrease in P62/SQSTM1 (p=0.0002) were noted, indicating the induction of autophagy flux in the add-on group. When GC+DSF-Cu treated mice were compared to the untreated tumour group, a substantial decrease in ALDH1/2 protein expression was observed (p= 0.0029 in IHC and p<0.0001 in western blot). Lipid peroxidation was significantly higher (p<0.0001) in the triple drug combination group than in untreated mice. There was a simultaneous decrease in reduced glutathione (GSH) and en-zyme superoxide dismutase (SOD) levels (p<0.0001), which strongly suggests the generation of reactive oxygen species and induction of ferroptotic cell death in the add-on therapy group. Additionally, in both IHC and western blot assays, ALDH1A3 expression was found to be significantly increased (p=0.0033, <0.0001 respectively) in GC+DSF-Cu treated mice relative to the untreated group, suggesting a potential connection between the ferroptosis pathway and ALDH1A3 overexpression.Conclusion:It was found that disulfiram with copper treatment inhibits bladder tumour growth through ferroptosis-mediated ROS induction, which further activates the process of autophagy. Our results prove that DSF-Cu can be an effective add-on therapy along with the standard chemotherapy drugs for the treatment of UBC.

2024-07-01·Biomedicine & Pharmacotherapy

The combination therapy using tyrosine kinase receptors inhibitors and repurposed drugs to target patient-derived glioblastoma stem cells

Article

作者: Lisiak, Natalia ; Pospieszna, Julia ; Rubis, Blazej ; Tang, Jing ; Murias, Marek ; Kucinska, Malgorzata ; Toton, Ewa

The lesson from many studies investigating the efficacy of targeted therapy in glioblastoma (GBM) showed that a future perspective should be focused on combining multiple target treatments. Our research aimed to assess the efficacy of drug combinations against glioblastoma stem cells (GSCs). Patient-derived cells U3042, U3009, and U3039 were obtained from the Human Glioblastoma Cell Culture resource. Additionally, the study was conducted on a GBM commercial U251 cell line. Gene expression analysis related to receptor tyrosine kinases (RTKs), stem cell markers and genes associated with significant molecular targets was performed, and selected proteins encoded by these genes were assessed using the immunofluorescence and flow cytometry methods. The cytotoxicity studies were preceded by analyzing the expression of specific proteins that serve as targets for selected drugs. The cytotoxicity study using the MTS assay was conducted to evaluate the effects of selected drugs/candidates in monotherapy and combinations. The most cytotoxic compounds for U3042 cells were Disulfiram combined with Copper gluconate (DSF/Cu), Dacomitinib, and Foretinib with IC₅₀ values of 52.37 nM, 4.38 µM, and 4.54 µM after 24 h incubation, respectively. Interactions were assessed using SynergyFinder Plus software. The analysis enabled the identification of the most effective drug combinations against patient-derived GSCs. Our findings indicate that the most promising drug combinations are Dacomitinib and Foretinib, Dacomitinib and DSF/Cu, and Foretinib and AZD3759. Since most tested combinations have not been previously examined against glioblastoma stem-like cells, these results can shed new light on designing the therapeutic approach to target the GSC population.

1

项与葡萄糖酸铜/双硫仑相关的新闻（医药）

2021-09-14

·BioSpace

Cantex Pharmaceuticals Announces Sale of Equity Interest in Chimerix, Inc.

WESTON, Fla., Sept. 14, 2021 /PRNewswire/ -- Cantex Pharmaceuticals ("Cantex") today announced that it has sold 6.5 million shares of Chimerix, Inc., in brokerage transactions at a price of $5.75 per share, less brokerage commissions and fees. About Cantex Pharmaceuticals Cantex Pharmaceuticals, Inc. is a privately-held, clinical stage pharmaceutical company focused on the transformation of known drugs into innovative products with blockbuster potential. Cantex is currently developing novel cancer treatments. Cantex's pipeline consists of three product candidates in Phase 2 and Phase 3 development for diseases with significant unmet medical needs: Azeliragon for life-threatening and disabling complications of cancer, Dicopp® for hematologic malignancies, and DSTAT, licensed to Chimerix, Inc., as a first-line therapy of acute myeloid leukemia. For more information, please visit . Cantex Contacts Investors: Stephen G. Marcus, M.D. (954) 315-3660 smarcus@cantex.com or Media: Jason Rando Tiberend Strategic Advisors (917) 930-6346 jrando@tiberend.com

100 项与葡萄糖酸铜/双硫仑相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
多形性胶质母细胞瘤	临床2期	美国	Washington University School of Medicine	2016-06-15
乳腺癌	临床2期	-	CANTEX, Inc.	-
胶质母细胞瘤	临床2期	-	CANTEX, Inc.	-
难治性多发性骨髓瘤	药物发现	美国	Cantex Pharmaceuticals, Inc.	2021-05-21
转移性胰腺癌	药物发现	美国	Cantex Pharmaceuticals, Inc.	2019-10-17
复发性胶质母细胞瘤	药物发现	美国	Cantex Pharmaceuticals, Inc.	2017-03-09
肝癌	药物发现	美国	University of Utah	2008-07-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03714555 (CTgov)	临床2期	转移性胰腺癌	1	AE Assessment+nab-paclitaxel (Abraxane)+Disulfiram/Copper Gluconate+gemcitabine (Gemzar) (Nab-Paclitaxel/Gemcitabine + DSF/Cu)	製簾繭網艱網齋構淵製(窪蓋顧廠壓夢鹹淵膚鹽) = 艱構網鹽築蓋餘醖鏇醖積衊簾顧蓋醖蓋獵蓋壓 (積齋網膚淵範範淵網鏇, 繭餘獵窪範構膚網鑰鑰 ~ 鹽鑰壓餘夢夢襯觸繭襯) 更多	-	2023-10-18
				AE Assessment+nab-paclitaxel (Abraxane)+Disulfiram/Copper Gluconate+gemcitabine (Gemzar) (FOLFIRINOX +DSF/Cu)	製簾繭網艱網齋構淵製(窪蓋顧廠壓夢鹹淵膚鹽) = 艱觸鹽鹹糧築醖築衊製積衊簾顧蓋醖蓋獵蓋壓 (積齋網膚淵範範淵網鏇, 壓築艱糧鹽選壓憲鹹鑰 ~ 顧顧鬱鹽衊鹽淵構鹹積) 更多
NCT03034135 (ACTR-21, CTgov)	临床2期	复发性胶质母细胞瘤	23	Temozolomide (TMZ)+Disulfiram/Copper	(淵遞網襯衊醖顧繭範網) = 築鹽獵鬱膚遞窪範窪鑰築廠襯鏇鏇壓齋廠觸鏇 (齋積構鑰範遞築鹽選憲, 積觸築襯選簾廠鏇夢餘 ~ 繭壓鏇製遞選簾窪網淵) 更多	-	2021-09-13
EXTH-61 (SNO2020)	N/A	复发性髓母细胞瘤 ALDH \| Nestin- \| CD133-positive	-	Disulfiram	製觸鏇餘壓衊衊願廠範(鑰網醖獵淵鑰廠鬱網鹽) = DSF/Cu++ induced cell death (increased AnnV/PI, cleaved-Poly(ADP-ribose)polymerase fraction, and Apoptosis Inducing Factor on WB/FC/IF, in vitro and ex vivo) through NPL4 accumulation in cell nucleus and intracellular buildup of poly-ubiquitylated proteins 衊簾簾構餘壓願鏇積顧 (艱鹽膚艱糧簾築憲壓膚 ) 更多	积极	2020-11-09
				Copper
PDTM-06 (SNO2019)	N/A	髓母细胞瘤	24	Disulfiram-Copper (DSF-Cu++)	遞觸繭膚網網鏇餘簾網(網獵獵鏇願顧簾夢製製) = 築鬱廠憲獵衊範壓鹹簾醖壓簾獵餘製鹹鑰觸襯 (醖選選遞鑰壓醖夢願淵 )	积极	2019-11-11
				Disulfiram-Copper (Control (No treatment))	遞觸繭膚網網鏇餘簾網(網獵獵鏇願顧簾夢製製) = 糧構遞鏇餘醖選簾鑰鬱醖壓簾獵餘製鹹鑰觸襯 (醖選選遞鑰壓醖夢願淵 )