Chemical genetics approaches for selective intervention in epigenetics.

In conventional chemical genetics, cell-active small-molecules directly block protein activity, altering phenotype. However these molecules may not be sufficiently selective or effective at modulating complex epigenetic pathways. By mutating the target protein, and creating a mutant-selective inhibitor, the bump-and-hole approach can provide single-target selectivity. PROTAC molecules direct their target to proteosomal degradation by recruiting an E3 ubiquitin ligase, resulting in more efficacious target downregulation.