Xenobiotic-activated receptors: from transcription to drug metabolism to disease

Chemical Research in Toxicology
Qiang Ma

Abstract

Xenobiotic-activated receptors (XARs) are a group of ligand-activated transcription factors that are evolutionally specialized to regulate genomic programs to protect the body against innumerable chemicals from the environment. XARs share unique properties, such as promiscuous ligand binding, conserved structural motifs, common protein partners, and overlapping target genes. These unique features of XARs clearly distinguish them from receptors that are activated by endogenous chemicals to regulate energy metabolism, reproduction, and growth and differentiation. XARs regulate xenobiotic metabolism and disposition by controlling the expression and induction of drug-metabolizing enzymes and transporters. Furthermore, XARs integrate a broad range of protective mechanisms, such as antioxidative response and immune/inflammatory functions, to antagonize foreign chemicals. As the primary means of xenobiotic sensing and defense, XARs are intimately involved in drug disposition, polymorphic drug clearance, drug-drug interaction, and pathogenesis of some chemically induced cancers and chronic diseases. As a consequence, some XAR characteristics have been exploited in drug development and safety evaluation of drugs and environmental carcin...Continue Reading

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Citations

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