ABSTRACT

Nature, as a biochemist, is unparalleled. Mankind has harvested the benefits of her combinatorial talents for thousands of years as a source of novel medicinals. For more than half a century, however, natural products have been relegated to source materials for ‘‘chemical libraries’’ from which new ‘‘leads’’ are mined (1). In a grants announcement, the National Institutes of Health (NIH) stated: ‘‘Chemical libraries are a mainstay of drug discovery. Well-crafted libraries, consisting of collections of anywhere from a few compounds to millions of them, can help scientists sort quickly through a haystack of possibilities to find the shining needle that may be developed into a lifesaving drug’’ (2). Once an ‘‘active’’ or ‘‘new chemical entity’’ (NCE), is found, it is isolated, ‘‘optimized,’’ and then screened in receptor assays for further clinical development. To enhance the odds of finding clinically useful NCEs, the pharmaceutical industry has developed modern techniques, which include proteomics, bioinformatics, ‘‘highthroughput’’ screening techniques, combinatorial chemistry, and computer-aided design and prediction of drug toxicity and metabolism. These new approaches are based upon increasing knowledge of receptor sites in normal and disease states.