Drug discovery technologies to identify and characterize modulators of the pregnane X receptor and the constitutive androstane receptor

The pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) are ligand-activated nuclear receptors (NRs) that are notorious for their role in drug metabolism, causing unintended drug-drug interactions and decreasing drug efficacy. They control the xenobiotic detoxification system by regulating the expression of an array of drug-metabolizing enzymes and transporters that excrete exogenous chemicals and maintain homeostasis of endogenous metabolites. Much effort has been invested in recognizing potential drugs for clinical use that can activate PXR and CAR to enhance the expression of their target genes, and in identifying PXR and CAR inhibitors that can be used as co-therapeutics to prevent adverse effects. Here, we present current technologies and assays used in the quest to characterize PXR and CAR modulators, which range from biochemical to cell-based and animal models.