Obtaining and screening compound collections: a user's guide and a call to chemists

Advances in genetics, proteomics and cell biology over the past 20 years have unearthed a multitude of potential macromolecular targets for the selective treatment of disease. The challenge remains to find appropriate small molecule ligands for these proteins (or nucleic acids), and to use these ligands to validate novel disease targets. The advent of low-cost instrumentation has made industrial-style high-throughput screening possible in academic settings. Unfortunately for many, access to large collections of compounds is still limited and limiting. This article is aimed at the user who has an interest in compound screening but does not have ready access to large collections of small molecules. High-throughput screening need not be the exclusive domain of institutions and centers with vast resources and NIH Roadmap-funded compound repositories. As it turns out, many of the most interesting compounds are probably within arm's reach, in our laboratory freezers and in those of our colleagues.