Metal based drugs: from serendipity to design
Metal based drugs: from serendipity to design
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DOI：
10.1039/b705551j
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发表时间：
2007-01-01
影响因子：
4
通讯作者：
Fricker, Simon Paul
中科院分区：
文献类型：
--
作者：
Fricker, Simon Paul
铂类抗癌药物顺铂对睾丸癌和卵巢癌的治疗做出了重大贡献。这一偶然发现刺激了对其他金属药物的研究。无机化学为药物化学提供了许多机会，金属药物的发现已经从偶然发现转向合理的药物设计。然而，药物发现和开发过程中存在许多挑战。本综述的目的是提供例证的作用，合理的药物设计在现代无机药物化学的背景下，这些挑战的案例历史。介绍了铂类药物从顺铂到第三代药物的演变。铂剂的分子靶标是DNA。提出了替代分子靶点，如含巯基蛋白质和氧化还原过程。综述了一种简单、安全、有效的金属基药物Fosrenol（TM）的例子。
The platinum anticancer drug cisplatin has made a major contribution to the treatment of testicular and ovarian cancer. This chance discovery has been the stimulus for research into other metal-based drugs. Inorganic chemistry offers many opportunities for medicinal chemistry, and the discovery of metal-based drugs has moved on from chance discovery to rational drug design. There are however, many challenges associated with the drug discovery and development process. The aim of this review is to provide case histories exemplifying the role of rational drug design in modern inorganic medicinal chemistry in the context of these challenges. The evolution of platinum drugs from cisplatin to third generation drugs is described. The molecular target for the platinum agents is DNA. Alternative molecular targets such as thiol-containing proteins and redox processes are proposed. The example of a simple, safe, efficacious metal-based drug, Fosrenol (TM), is reviewed.