Nuclear receptor subfamily 1 group I member 2 (NR1I2) (PXR)

The Nuclear receptor subfamily 1 group I member 2 (NR1I2), widely known as the Pregnane X receptor (PXR) or Steroid and xenobiotic receptor (SXR), is a key transcription factor that functions as a chemical sensor for the body [1.4.1, 1.4.3]. It is predominantly expressed in the liver and gastrointestinal tract, where it detects a broad range of exogenous xenobiotics and endogenous compounds like bile acids [1.2.3, 1.3.4]. When activated by a ligand, PXR heterodimerizes with the Retinoid X receptor (RXR) to upregulate genes involved in all phases of drug metabolism and transport, most notably the cytochrome P450 3A4 (CYP3A4) enzyme [1.1.1, 1.4.1]. This protective mechanism facilitates the detoxification and elimination of potentially harmful substances [1.2.1, 1.3.3]. However, PXR activation is also the primary molecular basis for many significant drug-drug interactions, as it can lead to the rapid clearance of other therapeutic agents [1.3.1, 1.3.2]. Additionally, PXR plays a role in metabolic homeostasis and inflammation, making it a target of interest for treating conditions such as cholestasis and inflammatory bowel disease [1.3.4, 1.4.4].

Other names

Pregnane X receptorSteroid and xenobiotic receptorSXRNR1I2Pregnane-activated receptorPARBenzoate X receptorBXROrphan nuclear receptor 1ONR1

PXR acts as a ligand-activated transcription factor that, upon binding to a variety of hydrophobic compounds, forms a heterodimer with the Retinoid X receptor (RXR) [1.4.1]. This complex binds to specific DNA response elements (e.g., DR3, ER6) in the promoter regions of target genes, inducing the expression of Phase I enzymes (CYP3A4, CYP2B6), Phase II enzymes (UGTs, SULTs), and Phase III transporters (MDR1, MRP2) [1.2.3, 1.3.4]. This coordinated induction enhances the detoxification and clearance of xenobiotics and endobiotics [1.3.1].