Zebrafish-Based Small Molecule Discovery

The earliest examples of small molecule discovery involved serendipitous phenotypic observations in whole organisms, but this organism-based process has given way in recent decades to systematic, high-throughput assays using purified proteins, cells, or cell extracts. In vitro screens have been successful at identifying modifiers of well-understood biological processes, but they are limited in their ability to discover modifiers of processes that are poorly understood or occur only in an integrated physiological context. Small model organisms, especially the zebrafish, make it possible to combine the advantages of organism-based small molecule discovery with the technologies and throughput of modern screening. The combination of model organisms with high-throughput screening is likely to extend small molecule discovery efforts to fields of study such as developmental biology and to broaden the range of diseases for which drug screening can be performed. [Copyright &y& Elsevier]