Chemical Genetics Hits "Reality"

Forward chemical genetic screening is analogous to the classical genetics strategy of mutagenesis, except that a small molecule takes the place of a genetic mutation in altering the function of one or more gene products. In their Perspective, Bellows and Tyers discuss an elegant forward chemical genetic screen that identifies small-molecule inhibitors called ubistatins that disrupt the cell9s protein degradation machinery ( Verma et al .). This work is an excellent example of the systematic identification of small-molecule inhibitors of complex biological processes and the characterization of their molecular targets.