Ligand- and structure-based pregnane X receptor models

Sandhya Kortagere; Matthew D Krasowski; Sean Ekins

doi:10.1007/978-1-62703-50-2_15

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Journal article

Ligand- and structure-based pregnane X receptor models

Sandhya Kortagere, Matthew D Krasowski and Sean Ekins

Methods in molecular biology (Clifton, N.J.), Vol.929, pp.359-375

2012

DOI: 10.1007/978-1-62703-50-2_15

PMID: 23007437

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Abstract

The human pregnane X receptor (PXR) is a ligand dependent transcription factor that can be activated by structurally diverse agonists including steroid hormones, bile acids, herbal drugs, and prescription medications. PXR regulates the transcription of several genes involved in xenobiotic detoxification and apoptosis. Activation of PXR has the potential to initiate adverse effects by altering drug pharmacokinetics or perturbing physiological processes. Hence, more reliable prediction of PXR activators would be valuable for pharmaceutical drug discovery to avoid potential toxic effects. Ligand- and protein structure-based computational models for PXR activation have been developed in several studies. There has been limited success with structure-based modeling approaches to predict human PXR activators, which can be attributed to the large and promiscuous site of this protein. Slightly better success has been achieved with ligand-based modeling methods including quantitative structure-activity relationship (QSAR) analysis, pharmacophore modeling and machine learning that use appropriate descriptors to account for the diversity of the ligand classes that bind to PXR. These combined computational approaches using molecular shape information may assist scientists to more confidently identify PXR activators. This chapter reviews the various ligand and structure based methods undertaken to date and their results.

Humans

Bayes Theorem

Models, Molecular

Receptors, Steroid - antagonists & inhibitors

Support Vector Machine

Receptors, Steroid - agonists

Quantitative Structure-Activity Relationship

Receptors, Steroid - chemistry

Details

Title: Subtitle: Ligand- and structure-based pregnane X receptor models
Creators: Sandhya Kortagere - Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA. Sandhya.Kortagere@drexelmed.edu
Matthew D Krasowski
Sean Ekins
Resource Type: Journal article
Publication Details: Methods in molecular biology (Clifton, N.J.), Vol.929, pp.359-375
Publisher: United States
DOI: 10.1007/978-1-62703-50-2_15
PMID: 23007437
ISSN: 1064-3745
eISSN: 1940-6029
Language: English
Date published: 2012
Academic Unit: Pathology
Record Identifier: 9984047772902771

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