Novel Functions of PXR - A Bioinformatic Approach. British Toxicology Society's Annual Congress. 2014.

The pregnane x receptor (PXR, NR1I2) is well established as being chiefly responsible for the coordinate regulation of xenobiotic metabolism. The promiscuous and prolific nature of the ligand binding domain is such that a wide variety of steroidal molecules will bind to, and activate the receptor. In recent years some interesting and novel roles for PXR have come to the forefront, with expression being confirmed in the vascular endothelium whereby it acts to mediate xenobiotic disposition through this vital tissue, and mediate oxidative stress (Swales, 2012). It is also apparent that PXR mediates expression of novel and interesting genes, such as Cdkn1A, Cdkn1b, Rbl2, Gas1, Serpine1, Plaur, Skp2 and Fbxw7 indicating a role in cell cycle and proliferation (Shizu, 2013).

In taking a bioinformatic approach to identifying novel roles of PXR, it is necessary to move away from the more traditional agonists, such as rifampicin, as the literature basis for these compounds focuses very heavily on their role in drug metabolism. Instead it was decided to use the isoquinoline alkaloid berberine as a basis for this search, as while this is a confirmed agonist of PXR the research surrounding the compound focusses on a wide range of cellular effects.