Applications of combinatorial technology to drug discovery

Abstract

Time- and cost-efficient approaches for combating new diseases is the guiding principle of modern medicine. New chemical entities are a critical requirement at the front end of drug discovery. In this context, combinatorial chemistry has emerged as a timely drug discovery tool. Through its enormous capacity to make available large numbers of different compounds in a very short period of time, combinatorial chemistry appears to be an ideal source for the discovery of novel drug entities against emerging disease targets. The continuing development of high throughput bioassay screening formats coupled with human genomics as a potential source of new biological targets creates an acute need for large numbers and types of diverse molecules. Conventional sources of chemicals do not bear the capacity to solve this crisis. The practical application of combinatorial chemistry to drug discovery is expected to fulfill this need, and hopefully in turn revert the problem by creating a demand for more efficient screening strategies. A continuing shift of challenges and synergism between chemistry, biology and automated instrumentation will soon bring us to previously unattainable levels of sophistication and efficiency in the area of novel drug discovery. Excellent reviews on combinatorial chemistry have appeared recently [1–6], and this chapter is confined to summarizing important applications of combinatorial chemistry to drug discovery through 1995, with major emphasis on non-peptidic molecules and small molecules.