The toxicogenomics of nuclear receptor agonists

Abstract

Toxicogenomics is the study of the structure and output of the genome as it responds to adverse xenobiotic exposure. Large-scale transcriptional analysis, made possible through microarray technologies, enables us to study and understand the complexity of the biological effects of drugs and chemicals, with the ultimate goal of separating wanted effects from adverse effects. Nuclear receptors are attractive targets for drug discovery because, as ligand-activated transcription factors, they coordinately regulate the expression of at least hundreds of genes that, in turn, control much of cellular metabolism. Through toxicogenomics, it is becoming possible to understand the therapeutic effects of agonists within the context of toxic effects, classify new chemicals as to their complete effects on biological systems, and identify environmental factors that may influence safety or efficacy of new and existing drugs.