from the conference included Target-Driven Approaches to Anticancer Agents, Pharmacokinetics for Medicinal Chemists, Recent Advances in the Structural Biology of Seven Transmembrane Receptors, and Nuclear Hormone Receptors. Professor Dale Boger (Scripps Research Institute) delivered the keynote address at this conference, highlighting synthetic and mechanistic aspects in his research on vancomycin, teicoplanin, and ramoplanin. This issue presents seminal papers from the symposia on Target-Driven Approaches to Anticancer Agent and Nuclear Hormone Receptors.
The symposium on Target-Driven Approaches to Anticancer Agents examined several recent advances in the oncology ®eld, with speci®c emphasis on new molecular targets. In recent years, there has been an explosion of novel targets in the oncology ®eld. Although this target-driven approach to new therapeutic agents has been the mainstay of the pharmaceutical industry for decades in other therapeutic areas, it is a relatively new approach to the discovery of anticancer agents. Historically, the search for new oncolytics has been a search for cytotoxic agents that can show some selectivity for cancer cells versus most normal cells. While the mechanistic understanding of these compounds typically followed, lead optimization efforts often focused on cytotoxicity endpoints, rather than inherent activity at the desired molecular target. This approach has frequently been successful in identifying exciting new compounds for preclinical studies, some healthy cells are usually affected. In fact, in many cases, the therapeutic indices of potential oncolytics are low, due to associated toxicity in normal tissues. By focusing on speci®c cellular targets that are active or up regulated only in cancer cells, it is hoped that more effective treatments can be developed. For example, inhibitors of receptor tyrosine kinases and cyclin-dependent kinase have recently been exploited and seem to be promising targets for therapeutic intervention. Two papers have been selected from this symposium to highlight the progress made so far in targeting kinases for the development of anticancer agents. They are from Dr. Peter L. Toogood at P®zer Global Research & Development and Dr. Peter Traxler and co-workers at Novartis Pharma AG.
The three papers from the symposium on Nuclear Hormone Receptors collectively re¯ect the leading edge of Nuclear Receptor research, bringing the sophisticated modern tools of both genomic pro®ling and structural biology to bear on a target class that has been a fruitful source of drugs for decades. The paper from Dr. Timothy Willson and his co-workers at GlaxoSmithKline is an impressive example of the use of chemical genomics not only to elucidate important biochemical mechanisms in the regulation of bile acid and cholesterol metabolism, but also as a springboard for 485