2002/10/01 by Steven A. Kliewer, Bryan Goodwin, Timothy M. Willson · 1 citation
Pharmacology, Toxicology and Pharmaceutics · Biochemistry, Genetics and Molecular Biology · Medicine · Chemistry · #Pharmacogenetics and Drug Metabolism #Estrogen and related hormone effects #Drug Transport and Resistance Mechanisms #Pregnane X receptor #Nuclear receptor #Xenobiotic #Constitutive androstane receptor #CYP3A4 #Drug metabolism #Pregnane #Chemistry #Biochemistry #Receptor #Ligand (biochemistry) #Pharmacology #Cytochrome P450 #Regulator #Biology #Metabolism #Gene #Transcription factor #Stereochemistry #Enzyme
paper · pdf · doi:10.1210/er.2001-0038
openalex publication_date 2002/10/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/31
The nuclear pregnane X receptor (PXR; NR1I2) is an important component of the body's adaptive defense mechanism against toxic substances including foreign chemicals (xenobiotics). PXR is activated by a large number of endogenous and exogenous chemicals including steroids, antibiotics, antimycotics, bile acids, and the herbal antidepressant St. John's wort. Elucidation of the three-dimensional structure of the PXR ligand binding domain revealed that it has a large, spherical ligand binding cavity that allows it to interact with a wide range of hydrophobic chemicals. Thus, unlike other nuclear receptors that interact selectively with their physiological ligands, PXR serves as a generalized sensor of hydrophobic toxins. PXR binds as a heterodimer with the 9-cis retinoic acid receptor (NR2B) to DNA response elements in the regulatory regions of cytochrome P450 3A monooxygenase genes and a number of other genes involved in the metabolism and elimination of xenobiotics from the body. Although PXR evolved to protect the body, its activation by a variety of prescription drugs represents the molecular basis for an important class of harmful drug-drug interactions. Thus, assays that detect PXR activity will be useful in developing safer prescription drugs.