Transcription factors: targets for new designer drugs.

Many diseases are the result of aberrant regulation of cell and tissue-specific gene expression. At the molecular level they are often characterised by disruption of the cell cycle through inappropriate activation or inactivation of key regulatory proteins, termed nuclear transcription factors (NFs). NF activation is modulated by several potent classes of drug, including steroids, retinoids, and immunosuppressants like cyclosporin A and FK506. While such drugs have wide application, they lack specificity and produce undesired side-effects. Recently, however, the three-dimensional structures of some NFs, as well as their molecular interactions with DNA targets, have been reported and several biochemical pathways involved in altered NF function identified. This is setting the stage for a rational approach to the design of drugs that act in a tissue- or disease-specific manner, target particular genes and proteins, and will combine increased efficacy with reduced side-effects.