Metal based drugs: from serendipity to design

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™, is reviewed.