Nuclear receptor subfamily 1 group I member 2 (Pregnane X receptor) (PXR)

The Nuclear receptor subfamily 1 group I member 2 (Pregnane X receptor, PXR) is a ligand-activated transcription factor that serves as a master regulator of xenobiotic and drug metabolism (UniProt O75469). Primarily expressed in the liver and intestines, PXR functions as a chemical sensor that detects a diverse array of synthetic drugs, environmental pollutants, and endogenous steroids (NCBI Gene 8856). Upon activation, it forms a heterodimer with the Retinoid X Receptor (RXR) to induce the expression of Phase I and Phase II metabolic enzymes, such as CYP3A4 and UGTs, as well as Phase III drug transporters like MDR1 (PMID: 11113130). While its primary biological role is detoxification and bile acid homeostasis, PXR is a critical factor in clinical pharmacology due to its role in mediating drug-drug interactions (PMID: 24048904). Therapeutic modulation of PXR is being explored for treating cholestatic liver diseases and inflammatory bowel disease, though its activation can also lead to unintended consequences like accelerated drug clearance or multi-drug resistance in cancer cells (PMID: 30114458). Furthermore, recent studies suggest PXR's involvement in broader metabolic processes, including lipid and glucose homeostasis, making it a complex target in metabolic syndrome and oncology (PMID: 33065333).

Other names

Steroid and xenobiotic receptorSXRPregnane X receptorNR1I2Pregnane X nuclear receptorPARPAR1PAR2BXRONR1

Ligand-induced activation followed by heterodimerization with Retinoid X Receptor (RXR) to regulate the transcription of genes involved in xenobiotic detoxification and transport, such as CYP3A4 and MDR1.