Machine learning-based models for high-throughput classification of human pregnane X receptor activators
نویسندگان
چکیده
The pregnane X receptor (PXR) is a master in regulating the metabolism and transport of structurally diverse endogenous compounds. Activation PXR by xenobiotics potentially induces adverse effects and...
منابع مشابه
Predicting Rat and Human Pregnane X Receptor Activators Using Bayesian Classification Models.
The pregnane X receptor (PXR) is a ligand-activated transcription factor that acts as a master regulator of metabolizing enzymes and transporters. To avoid adverse drug-drug interactions and diseases such as steatosis and cancers associated with PXR activation, identifying drugs and chemicals that activate PXR is of crucial importance. In this work, we developed ligand-based predictive computat...
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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 nor...
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Pregnane X receptor (PXR) regulates drug metabolism and is involved in drug-drug interactions. Prediction of PXR activators is important for evaluating drug metabolism and toxicity. Computational pharmacophore and quantitative structure-activity relationship models have been developed for predicting PXR activators. Because of the structural diversity of PXR activators, more efforts are needed f...
متن کاملInduction of ABCC3 (MRP3) by pregnane X receptor activators.
The pregnane X receptor (PXR) mediates the induction of various genes by xenobiotics, including several ATP-binding cassette transporters. PXR is also activated by bile acids likely to prevent their accumulation to toxic levels; however, the role of PXR in the regulation of MRP3, an important bile acid efflux transporter, has not been elucidated. The impact of PXR activators on the hepatic expr...
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In this report we show that submicromolar concentrations of dexamethasone enhance pregnane X receptor (PXR) activator-mediated CYP3A4 gene expression in cultured human hepatocytes. Because this result is only observed after 24 h of cotreatment and is inhibited by pretreatment with cycloheximide, we further investigated which factor(s), induced by dexamethasone, might be responsible for this eff...
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ژورنال
عنوان ژورنال: Environmental science
سال: 2023
ISSN: ['2634-3606']
DOI: https://doi.org/10.1039/d2va00182a