Forward chemical genetics: progress and obstacles on the path to a new pharmacopoeia.
Forward chemical genetics is a new method to systematize the discovery and use of small molecules as tools for basic biological research. This approach requires three basic components: a library of compounds; an assay, in which the library is screened for a cellular or organismal phenotype; and a method to trace an active compound to its biological target. Bioactive compounds have traditionally been isolated from natural product extracts, although 'diversity-oriented synthesis' and commercial compound collections are gaining in prominence. New techniques, such as image-based screening and the cytoblot method, have increased the throughput of phenotypic assays. Strategies are also being developed to streamline target identification using molecular biological approaches.
Lokey
R Scott
RS
Department of Chemistry and Biochemistry, University of California Santa Cruz, Santa Cruz, CA 95064, USA. lokey@chemistry.ucsc.edu
D004353:Drug Evaluation, Preclinical / Q000379:methods*; D008967:Molecular Biology / Q000379:methods*; D015335:Molecular Probes; D010602:Pharmacopoeias as Topic
D015335:Molecular Probes