Enhancing drug discovery by acquisition of chemical diversity

Publisher Summary One of the key parameters influencing the productivity of high throughput screens, in pharmaceutical drug discovery, is the chemical diversity of the compounds that are tested. Large pharmaceutical companies have significant collections of historical compounds at their disposal and continue to make more by conventional and combinatorial chemistries. The chapter examines the growth of the compound collection, used for screening in GlaxoWellcome, during the period 1996–2000; and discusses the internal drivers for expanding the compound collection and describes how to develop a rationale for compound acquisition as a means of achieving this. During the past ten or more years, the process of drug discovery in pharmaceutical companies has undergone many radical changes. There has been a move away from pharmacology-based testing of small numbers of compounds (often analogues of the natural ligand), generated by conventional medicinal chemistry, toward what is now understood as high throughput screening (HTS). The development of HTS has led to a demand for companies to have significant numbers of appropriate samples for screening at their disposal. One of the potential advantages of the random approach to screening is that one can identify activity with novel chemotypes that had not previously been associated with the particular biological target. There is thus a considerable onus on the screening organization to greatly enhance, on a continuing basis, the chemical diversity of its screening collection.