Ecology & Safety, Volume 9, 2015

Abstract: The nuclear receptor member human pregnane X receptor (hPXR) regulates enzymes and transporters involved in xenobiotic detoxification as well as maintains homeostatic balance of bile acids, thyroid and steroid hormones. hPXR can be recognized and activated by a structurally diverse array of environmental chemicals and drug compounds to initiate adverse biological effects, such as perturbing normal physiological functions and causing dangerous drug–drug interactions and exhibiting a high promiscuity in its ligand spectrum. In the current study capabilities for structure-activity modeling incorporated in the platform QSAR Toolbox were employed for investigation the binding mode and structural basis of hPXR interactions with various activators and non-activators. A total of 348 molecules, representing a variety of chemical structures, constituted the training set of the model. Validation of the model showed a sensitivity of 70%, a specificity of 85%, and a concordance of 77%. The developed model provide knowledge about molecular descriptors that may influence the effect of molecules to hPXR.