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Toxicologic Pathology, Vol. 29, No. 1, 3-5 (2001)
DOI: 10.1080/019262301301418801

Regulation of Xenobiotic Metabolism by Orphan Nuclear Receptors

Richard T. Miller

Department of Pathology Glaxo Weitcome Researrch & Development, Research Friangle Park, North Carolina 27709

Timothy M. Willson

Department of Medicinal Chemistry, Glaxo Wellcome Research & Development, Research Triangle Park, North Carolina 27709

Nuclear receptors control gene transcription by binding to specifi cpromoter regions of DNA in the presence of ligand. Orphan nuclear receptors are nuclear receptors for which the endogenous ligand(s) has yet to be identified. Systematic evaluation of orphan nuclear receptors can elucidate species differences in xenobiotic metabolism in addition to aiding in identification of endogenous ligands. The receptor-binding affinity and specifi city of various chemicals, with subsequent determination of the genes controlled by nuclear receptors, are goals of investigations into orphan nuclear receptor structure/function and can provide valuable tools in predicting drug interactions and toxicity.

Key Words: Drug-drug interaction • pregnane X receptor • peroxisome proliferator • St. John's wort


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