Pregnane X Receptor (PXR) Nuclear Receptor Assay Service

Unlocking Potential: Precision PXR Assays with Creative Biolabs

Predominantly expressed in the liver and intestines, the pregnane X Receptor (PXR) regulates the expression of essential detoxifying enzymes like cytochrome P450s (CYPs) and drug transporters. Nuclear receptor assays are vital gear in biomedical research, permitting scientists to take a look at the binding affinity, activity, and functionality of those receptors. These assays are used to screen for brand-spanking new drug applicants, apprehend receptor-ligand interactions, and look at the molecular mechanisms underlying numerous diseases. Accurate and reliable nuclear receptor assays offer essential facts that power the development of new therapeutics and beautify our information on disorder pathology.

Creative Biolabs is delighted to introduce our PXR nuclear receptor assay service, demonstrating our commitment to excellence and expertise in this field. With a focus on delivering precise and high-quality data, we offer comprehensive solutions for studying the human PXR or rat PXR receptors.

• Assay Information:

Our PXR nuclear receptor assay service employs a functional, cell-based approach tailored to investigate both agonist and antagonist activities. We utilize advanced methodologies to detect IC50 values, offering detailed assessments of compound potency and efficacy against the PXR receptor.

The PXR nuclear receptor assay plays a pivotal role in understanding and predicting drug metabolism and pharmacokinetics through its interaction with absorption, distribution, metabolism, and excretion (ADME) processes. This connection is critical for optimizing drug candidates, improving bioavailability, and ensuring efficacy while minimizing adverse effects. Creative Biolabs' specialized PXR nuclear receptor assay service offers precise insights into these interactions, empowering pharmaceutical research to develop safer and more effective therapeutics.

Workflow

1. Cell Line Preparation
   • Culture and Maintenance: Cells expressing human or rat PXR receptors are cultured under optimized conditions to ensure viability and consistency.
2. Assay Arrangement
   • Plate Seeding: Cells are seeded into multi-well plates suitable for high-throughput screening, ensuring uniform distribution and optimal assay conditions.
   • Compound Treatment: Test compounds, including potential agonists and antagonists, are prepared at varying concentrations for dose-response analysis.
3. Incubation and Stimulation
   • Cells are treated with test compounds to assess their effects on PXR receptor activity. Agonist assays measure receptor activation levels, while antagonist assays evaluate inhibition.
4. Detection and Measurement
   • Reporter Gene Assay: Following incubation, reporter gene assays are performed to quantify PXR-mediated transcriptional activity.
   • IC50 Determination: Dose-response curves are analyzed to determine IC50 values, indicating the concentration of compounds required for half-maximal activation or inhibition of PXR.

Published Data

This figure illustrates the dose-response relationships of these compounds, highlighting their varying potencies and efficacies in activating the PXR. Each curve represents the activity of a compound across a range of concentrations, making an allowance for the identification of both potent agonists and partial agonists inside the institution. The figure underscores the importance of structure-activity relationship (SAR) analysis in understanding how subtle changes in compound structure can affect PXR activation. This information is crucial for optimizing lead compounds in drug development, ensuring effective modulation of PXR activity for therapeutic purposes.

Fig.1 Activity response curves from a group of structurally similar compounds.¹

Applications

• Assessing the effects of compounds on PXR activation to predict their influence on drug metabolism pathways.
• Identifying potential inducers or inhibitors of PXR-regulated enzymes, such as cytochrome P450s (CYPs), is crucial for drug clearance.
• Evaluating how candidate drugs may interact with existing medications via PXR-mediated pathways.
• Screening compounds for their potential to induce or inhibit PXR, influencing drug safety profiles and toxicological outcomes.
• Identifying compounds that may lead to liver toxicity through PXR-regulated pathways.
• Predicting drug clearance rates and dosage adjustments based on PXR activation levels.

Advantages

• Deep expertise in PXR biology, ensuring accurate and insightful assay interpretations.
• Utilization of state-of-the-art cell-based assay platforms for high-throughput screening and precise detection of PXR activation.
• Integration of functional assays to assess both agonist and antagonist effects on PXR

PXR nuclear receptor assay service stands as an indispensable tool for researchers seeking to advance their understanding of the drug metabolism mediated by PXR. Contact us today to leverage our expertise and resources in PXR nuclear receptor assays.

Reference

1. Lynch, Caitlin, et al. "Quantitative high-throughput identification of drugs as modulators of human constitutive androstane receptor." Scientific reports 5.1 (2015): 10405.

For Research Use Only | Not For Clinical Use