旧的铜结合药物的新用途：将促血管生成的铜转化为特定的癌细胞死亡诱导剂。
New uses for old copper-binding drugs: converting the pro-angiogenic copper to a specific cancer cell death inducer.
作者信息
Chen Di, Dou Q Ping
机构信息
Wayne State University, The Prevention Program, Barbara Ann Karmanos Cancer Institute, Department of Pathology, School of Medicine, Detroit, Michigan, USA.
出版信息
Expert Opin Ther Targets. 2008 Jun;12(6):739-48. doi: 10.1517/14728222.12.6.739.
Abstract
BACKGROUND
The conventional approach toward anticancer drug development is a time-consuming and expensive procedure.
OBJECTIVE/METHODS: One approach to expedite this process and achieve more affordable means is to discover new applications of existing drugs, since their pharmacokinetics and pharmacological profiles are well known.
RESULTS
Our encouraging findings in recent studies reveal anticancer activities of several copper-binding ligands including disulfiram (an antialcoholism drug), clioquinol (used to treat Alzheimer's and Huntington's diseases) and diethyldithiocarbamate (an agent for HIV-1 infection treatment).
CONCLUSION
These in vitro and in vivo studies have demonstrated that these archaic drugs can target and react with tumor cellular copper, forming complexes that act as potent proteasome inhibitors and apoptosis inducers.
摘要
背景
传统的抗癌药物研发方法既耗时又昂贵。
目的/方法：加快这一过程并实现更经济实惠方法的一种途径是发现现有药物的新用途，因为它们的药代动力学和药理学特征是已知的。
结果
我们近期研究中令人鼓舞的发现揭示了几种铜结合配体的抗癌活性，包括双硫仑（一种戒酒药物）、氯碘羟喹（用于治疗阿尔茨海默病和亨廷顿病）和二乙基二硫代氨基甲酸盐（一种用于治疗HIV-1感染的药物）。
结论
这些体外和体内研究表明，这些古老的药物可以靶向肿瘤细胞铜并与之反应，形成作为有效蛋白酶体抑制剂和凋亡诱导剂的复合物。
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