Human Transporter BCRP Inhibition Assessment Service
Introduction
Breast Cancer Resistance Protein (BCRP), encoded by the ABCG2 gene, is an ATP-binding cassette (ABC) efflux transporter known for its significant role in limiting the absorption and enhancing the excretion of various xenobiotics, including therapeutic drugs. BCRP is highly expressed in barrier tissues such as the gastrointestinal tract, liver, kidneys, blood-testis barrier, blood-brain barrier, and mammary glands. Its inhibition can consequently lead to increased systemic exposure to drugs, leading to potential drug-drug interactions (DDIs). Understanding the BCRP inhibition potential of new drug candidates is thus critical in drug development and safety assessment.
Our Human Transporter BCRP Inhibition Assessment Service
At Creative Biolabs, we bring over 20 years of experience in the biotechnology field to deliver precise and regulatory-compliant human transporter BCRP inhibition assessment services. Our services are designed to meet the stringent guidelines ensuring reliable and predictive data for both early-stage screening and later-stage regulatory studies.
Service Details
Assay Types
Creative Biolabs uses both cell-based and vesicle-based assays to evaluate BCRP inhibition:
Cell-Based Assays: We utilize polarized monolayer systems, such as MDCKII-BCRP cells, allowing for the measurement of active efflux across the cell monolayer. This method involves bi-directional transport assays to determine the apical to basal transport of substrates, effectively identifying the inhibitory potential of test compounds.
Vesicle-Based Assays: When dealing with compounds exhibiting low passive permeability, BCRP-expressing inside-out vesicles derived from HEK293 cells are employed. These vesicles allow for the assessment of drug uptake inhibition by monitoring the internalization of a known BCRP substrate such as Estrone 3-sulfate.
Testing Parameters
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Substrate: Estrone 3-sulfate
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Detection Method: High-Performance Liquid Chromatography coupled with Tandem Mass Spectrometry (HPLC-MS/MS)
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Data Analysis and Interpretation
High-quality data is obtained, which includes IC50 determination for quantitative analysis of BCRP inhibition. Creative Biolabs ensures that every step from data collection to interpretation adheres to industry standards and best practices, providing comprehensive reports to support your drug development endeavors.
Features of the Service
Regulatory Compliance
Our services are fully aligned with the recommendations outlined by international regulatory bodies. This compliance ensures that your drug candidates meet global regulatory requirements, facilitating smoother approval processes.
Precision and Reliability
Creative Biolabs' BCRP inhibition assessment is conducted utilizing precise assays that offer reproducible and reliable results. Our state-of-the-art facilities and seasoned experts ensure consistency with industry protocols, delivering high confidence in data outcomes.
Diverse Assay Platforms
By offering both cell-based and vesicle-based assays, Creative Biolabs accommodates a range of compounds, including those with low membrane permeability, thereby reducing the risk of false negatives and providing a comprehensive evaluation of BCRP inhibition.
Scientific Backing
Studies have shown several ABCG2 inhibitor agents for hyperuricemia globally used in clinical situations. For instance, Febuxostat has demonstrated significant inhibition of BCRP than Ko143 and elacridar using the vesicle transport assay.
Fig.1 Inhibitory effect of febuxostat against ABCG2 compared with the inhibitors Ko143 and elacridar.1,2
Frequently Asked Questions
Q1: Why are both cell-based and vesicle-based assays offered?
A1: Offering both approaches allows us to accommodate a broad spectrum of compounds, particularly those with differing permeability properties, ensuring a robust and accurate assessment of BCRP inhibition potential.
Q2: What is the significance of BCRP inhibition for drug development?
A2: BCRP inhibition can significantly alter the pharmacokinetics of drugs, leading to increased exposure and potential DDIs. Understanding these effects early in drug development is crucial for optimizing dosing regimens and ensuring patient safety.
Creative Biolabs is your trusted partner for comprehensive Human Transporter BCRP Inhibition Assessment Services. Our expertise, advanced technologies, and commitment to quality deliver the data necessary to drive your project's success. Contact us today to see how we can support your drug development needs, ensuring regulatory compliance and enhancing the safety profile of your drug candidates.
References
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Toyoda, Yu, Tappei Takada, and Hiroshi Suzuki. "Inhibitors of human ABCG2: from technical background to recent updates with clinical implications." Frontiers in pharmacology 10 (2019): 208.
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Distributed under Open Access License CC BY 4.0, without modification.
For Research Use Only | Not For Clinical Use
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