Drug screens using the nematode Caenorhabditis elegans

Since its inception as a model system, Caenorhabditis elegans has provided insight about the mechanism of action of drugs through genetic analyses. With the arrival of diverse drug-like small molecule libraries sometime later, the worm also became a platform for drug discovery that was previously inaccessible to academics. Here, the history of larger-scale drug screens using C. elegans is reviewed. The current approaches used to identify the targets and targeted pathways of the novel hits from these screens are also discussed. We focus on the development of small molecule tools for biological investigation, the discovery of novel candidate nematicides and anthelmintics, and touch on screens related to other areas of biology, including neurodegeneration. Finally, we draw attention to the fundamental aspects of C. elegans biology that lends itself to chemical genetic research. When combined with diverse small molecule libraries, the worm's tractability and genetic power make it an unparalleled whole-animal model system for early-stage drug discovery.