Cu(II)ATSM(Cu(II)ATSM) - _专利_临床

概要

基本信息

药物类型

小分子化药

别名

Copper(II)-diacetyl-di(N4-methylthiosemicarbazone)、Cu-ATSM、Cu-diacetyl-bis(N4-methylthiosemicarbazonate)

+ [2]

靶点-

作用机制

神经元调节剂

治疗领域

神经系统疾病内分泌与代谢疾病其他疾病

在研适应症-

非在研适应症

肌萎缩侧索硬化帕金森病

原研机构

University of Melbourne

在研机构-

非在研机构

Collaborative Medicinal Development LLC

最高研发阶段无进展临床3期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

登录后查看时间轴

关联

9

项与 Cu(II)ATSM 相关的临床试验

NCT04313166 / Completed临床2期

A Treatment Continuation Study for Patients With Amyotrophic Lateral Sclerosis/Motor Neuron Disease Who Have Successfully Complete Study CMD-2019-001

Provides up to six months treatment with CuATSM for subjects who have successfully completed study CMD-2019-001

开始日期2020-03-19

申办/合作机构

Collaborative Medicinal Development LLC

NCT04082832 / Unknown status临床2/3期

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of Cu(II)ATSM in Patients With Amyotrophic Lateral Sclerosis/Motor Neuron Disease

Multicenter, randomized, double-blind, placebo controlled study to assess the tolerabilty and efficacy of CuATSM in patients with ALS/MND. Patients will be randomized 1:1 to CuATSM or placebo for 6 x 28-day cycles (24 weeks) of treatment.

开始日期2019-09-30

申办/合作机构

Collaborative Medicinal Development LLC

EUCTR2018-002079-17-FR / Unknown status临床2期

Evaluation of the 64Cu-ATSM PET-CT as a predictor of the response to neo-adjuvant treatment in locally advanced rectal cancers - TEP-64Cu-ATSM-Rectum

开始日期2018-10-16

申办/合作机构

Institut de Cancérologie de l'Ouest (ICO)

100 项与 Cu(II)ATSM 相关的临床结果

登录后查看更多信息

100 项与 Cu(II)ATSM 相关的转化医学

登录后查看更多信息

100 项与 Cu(II)ATSM 相关的专利（医药）

登录后查看更多信息

151

项与 Cu(II)ATSM 相关的文献（医药）

2023-10-01·American Journal of Physiology-Lung Cellular and Molecular Physiology

IL-17A neutralization fails to attenuate airway remodeling and potentiates a proinflammatory lung microenvironment in diacetyl-exposed rats

Article

作者: Chalupa, David ; Johnston, Carl J. ; House, Emma L. ; Hernady, Eric ; McGraw, Matthew D. ; Groves, Angela M. ; Kim, So-Young

Interleukin-17A (IL-17A) neutralization has shown benefit previously in preclinical models of transplant-associated bronchiolitis obliterans (BO), yet it remains unknown whether IL-17A neutralization has similar benefit for other forms of BO. Here, IL-17A neutralization fails to prevent severe airway remodeling in rats exposed repetitively to the flavoring chemical diacetyl, and instead, promotes a proinflammatory microenvironment with increased expression of TNF-α, IL-1β, and NF-κB within the lung.

2023-05-10·Diagnostics (Basel, Switzerland)

Feasibility of Renal Blood Flow Measurement Using ⁶⁴Cu-ATSM PET/MRI: A Quantitative PET and MRI Study.

Article

作者: Iwano, Masayuki ; Takahashi, Naoki ; Mori, Tetsuya ; Tsujikawa, Tetsuya ; Okazawa, Hidehiko ; Nishikawa, Yudai ; Kiyono, Yasushi ; Kimura, Hideki ; Kobayashi, Mamiko ; Nishimori, Kazuhisa ; Nishikawa, Sho ; Kasuno, Kenji ; Shimamoto, Yuki

This study aimed to evaluate the renal blood flow (RBF) in patients with chronic kidney disease (CKD) using ⁶⁴Cu(II)-diacetyl-bis(4-methylthiosemicarbazonate) (⁶⁴Cu-ATSM) for positron emission tomography (PET)/magnetic resonance imaging (MRI). We included five healthy controls (HCs) and ten patients with CKD. The estimated glomerular filtration rate (eGFR) was calculated from the serum creatinine (cr) and cystatin C (cys) levels. The estimated RBF (eRBF) was calculated using the eGFR, hematocrit, and filtration fraction. A single dose of ⁶⁴Cu-ATSM (300-400 MBq) was administered for RBF evaluation, and a 40 min dynamic PET scan was performed with simultaneous arterial spin labeling (ASL) imaging. PET-RBF images were obtained from the dynamic PET images at 3 min after injection using the image-derived input function method. The mean eRBF values calculated from various eGFR values differed significantly between the patients and HCs; both groups also differed significantly in terms of the RBF values (mL/min/100 g) measured using PET (151 ± 20 vs. 124 ± 22, p < 0.05) and ASL-MRI (172 ± 38 vs. 125 ± 30, p < 0.001). The ASL-MRI-RBF was positively correlated with the eRBFcr-cys (r = 0.858, p < 0.001). The PET-RBF was positively correlated with the eRBFcr-cys (r = 0.893, p < 0.001). The ASL-RBF was positively correlated with the PET-RBF (r = 0.849, p < 0.001). ⁶⁴Cu-ATSM PET/MRI demonstrated the reliability of PET-RBF and ASL-RBF by comparing them with eRBF. This is the first study to demonstrate that ⁶⁴Cu-ATSM-PET is useful for assessing the RBF and is well correlated with ASL-MRI.

2023-02-01·Cell Death & Differentiation

Ferroptotic stress facilitates smooth muscle cell dedifferentiation in arterial remodelling by disrupting mitochondrial homeostasis

Article

作者: Zhang, Guo-Yan ; Zhang, Jia-Bao ; Wang, Xu-Jie ; Zhang, Zhen ; Wang, Pei ; Lu, Jin-Jian ; Wu, Wen-Bin ; Sun, Di-Yang ; Li, Dong-Jie ; Tong, Jie ; Zeng, Fei-Yan ; Ji, Qing-Xin ; Shen, Fu-Ming ; Zhou, Jian ; Cao, Wen-Xiang

Smooth muscle cell (SMC) phenotypic switch from a quiescent 'contractile' phenotype to a dedifferentiated and proliferative state underlies the development of cardiovascular diseases (CVDs); however, our understanding of the mechanism is still incomplete. In the present study, we explored the potential role of ferroptosis, a novel nonapoptotic form of cell death, in SMC phenotypic switch and related neointimal formation. We found that ferroptotic stress was triggered in cultured dedifferentiated SMCs and arterial neointimal tissue of wire-injured mice. Moreover, pro-ferroptosis stress was activated in arterial neointimal tissue of clinical patients who underwent carotid endarterectomy. Blockade of ferroptotic stress via administration of a pharmacological inhibitor or by global genetic overexpression of glutathione peroxidase-4 (GPX4), a well-established anti-ferroptosis molecule, delayed SMC phenotype switch and arterial remodelling. Conditional SMC-specific gene delivery of GPX4 using adreno-associated virus in the carotid artery inhibited ferroptosis and prevented neointimal formation. Conversely, ferroptosis stress directly triggered dedifferentiation of SMCs. Transcriptomics analysis demonstrated that inhibition of ferroptotic stress mainly targets the mitochondrial respiratory chain and oxidative phosphorylation. Mechanistically, ferroptosis inhibition corrected the disrupted mitochondrial homeostasis in dedifferentiated SMCs, including enhanced mitochondrial ROS production, dysregulated mitochondrial dynamics, and mitochondrial hyperpolarization, and ultimately inhibited SMC phenotypic switch and growth. Copper-diacetyl-bis^N4-methylthiosemicarbazone (CuATSM), an agent used for clinical molecular imaging and that potently inhibits ferroptosis, prevented SMC phenotypic switch, neointimal formation and arterial inflammation in mice. These results indicate that pro-ferroptosis stress is likely to promote SMC phenotypic switch during neointimal formation and imply that inhibition of ferroptotic stress may be a promising translational approach to treat CVDs with SMC phenotype switch.

100 项与 Cu(II)ATSM 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

登录

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
肌萎缩侧索硬化	临床3期	澳大利亚	Collaborative Medicinal Development LLC	2019-09-30
帕金森病	临床3期	澳大利亚	Collaborative Medicinal Development LLC	2017-08-14

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


CMD-2016-001 \| CuATSM (AAN2020)	临床2期	肌萎缩侧索硬化	15	CuATSM	蓋觸淵簾淵蓋艱鑰淵願(顧襯廠衊壓構鹽遞衊壓) = 遞構繭遞構壓衊鹽製憲壓衊鬱構構壓憲夢網積 (糧網鏇網蓋衊蓋餘艱選 )	积极	2020-04-14