Abstract
Pregnane X Receptor (PXR), a member of the nuclear receptor (NR) superfamily, is expressed in liver and intestine, as also in other tissues and cells. PXR is activated by a wide variety of endobiotics, dietary compounds and pharmaceuticals. This nuclear receptor serves as a master transcriptional regulator of CYP3A isozymes, and also regulates a large number of enzymes and transporters involved in the pharmacokinetics of both endobiotics and xenobiotics. PXR has an impact on energy homeostasis through glucose and lipid metabolism regulation. PXR activation is also hepatoprotective against toxic bile acids. New roles for PXR have been identified in bone homeostasis, inflammatory bowel disease, liver steatosis and fibrogenesis. PXR directly regulates the expression of multidrug resistance protein 1 (MDR1) and other important proteins involved in drug metabolism. Drug-drug interactions can affect patients with cardiovascular disease, tuberculosis, HIV and cancer. Especially cancer patients are at high risk of such interactions, as treated with multi-drug combinations. PXR activation can affect the efficacy of chemotherapeutics, thus targeting PXR may represent a novel strategy for the improvement of the pharmacokinetics of chemotherapeutic agents, thereby providing safer and more effective therapies for cancer patients.
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