Journal
DRUG METABOLISM REVIEWS
Volume 38, Issue 3, Pages 515-597Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/03602530600786232
Keywords
pregnane-X-receptor; constitutive androstane receptor; cytochrome P450; CYP2B; CYP3A; null mice; humanised mice; transcription factors
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Xenobiotic metabolism and detoxification is regulated by receptors (e.g., PXR, CAR) whose characterization has contributed significantly to our understanding of drug responses in humans. Technologies facilitating the screening of compounds for receptor interactions provide valuable tools applicable in drug development. Most use in vitro systems or mice humanized for receptors in vivo. In vitro assays are limited by the reporter systems and cell lines chosen and are uninformative about effects in vivo. Humanized mouse models provide novel, exciting ways of understanding the functions of these genes. This article evaluates these technologies and current knowledge on PXR/CAR-mediated regulation of gene expression.
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