PXR Activators

PXR activators are compounds that stimulate the activity or enhance the expression of the pregnane X receptor (PXR). PXR, also known as NR1I2 (nuclear receptor subfamily 1, group I, member 2), is a nuclear receptor that functions as a ligand-activated transcription factor. It is primarily expressed in the liver and intestines, and its main role is to sense the presence of foreign toxic substances and support the body's detoxification process by regulating genes involved in drug metabolism and transport. The ligand-binding domain of PXR has a notably flexible structure, allowing it to bind to a wide variety of endogenous and exogenous molecules, including prescription drugs, dietary supplements, and environmental contaminants. Upon ligand binding, PXR undergoes a conformational change that leads to its activation. The activated PXR forms a heterodimer with the retinoid X receptor (RXR) and then binds to specific DNA sequences, termed PXR response elements, to modulate the transcription of target genes. These target genes are often involved in drug metabolism and drug transport. PXR activators, by engaging with the receptor, can potentiate these regulatory effects, influencing the body's capacity to metabolize and excrete foreign compounds. The study of PXR activators provides insights into the body's adaptive mechanisms for responding to xenobiotic exposure. This understanding underscores the body's remarkable ability to recognize, process, and eliminate a myriad of diverse compounds, ensuring homeostasis and protection against toxic threats.