Targeting xenobiotic receptors PXR and CAR in human diseases

•PXR and CAR regulate drug disposition and human diseases.•PXR and CAR are potential drug targets.•Small molecules modulating specific function of PXR or CAR are needed.•We propose approaches to target PXR and CAR.•We discuss the challenges in targeting PXR and CAR. Nuclear receptors such as the pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are xenobiotic receptors regulating not only drug metabolism and disposition but also various human diseases such as cancer, diabetes, inflammatory disease, metabolic disease and liver diseases, suggesting that PXR and CAR are promising targets for drug discovery. Consequently, there is an urgent need to discover and develop small molecules that target these PXR- and/or CAR-mediated human-disease-related pathways for relevant therapeutic applications. This review proposes approaches to target PXR and CAR, either individually or simultaneously, in the context of various human diseases, taking into consideration the structural differences between PXR and CAR.