Background of BSEP and BSEP Inhibition

The Bile Salt Export Pump (BSEP, also known as ABCB11) plays a crucial role in human hepatic physiology. As an ATP-binding cassette (ABC) transporter, BSEP is essential for the transport of bile acids from hepatocytes into the bile canaliculus. Any disruption or inhibition of BSEP activity can trigger hepatic conditions such as cholestasis and drug-induced liver injury (DILI). With approximately 70% of drugs being eliminated via the liver, it's essential to understand the mechanisms behind BSEP inhibitors to mitigate risks of liver damage. Creative Biolabs has developed a robust fluorescence-based inhibition assay, harnessing our decades of experience and advanced technological capability.

Fig.1 Topology structure of human BSEP.^1,2

Human Transporter BSEP Fluorescence-Based Inhibition Assay Service at Creative Biolabs

Creative Biolabs offers an advanced fluorescence-based inhibition assay specifically designed for the BSEP transporter. This service is tailored to provide high-quality, reproducible data critical for early-stage drug screening and later-stage regulatory studies. Our assay leverages the sensitivity and cost efficiency of fluorescent probes, presenting a reliable alternative to traditional radioligand assays. Furthermore, this assay aligns with guidance from regulatory bodies ensuring compliance and reliability in data reporting.

Application Fields of Human Transporter BSEP Fluorescence-Based Inhibition Assay

• Early-stage Screening

Initial evaluation of compound libraries to identify potential BSEP inhibitors before proceeding to more advanced studies.

• Regulatory Safety Testing

In line with guidelines from EMA, PMDA, and ICH, proactive screening of BSEP inhibition to preemptively address potential DILI risks.

• Mechanistic Toxicology

Investigating the mechanisms by which xenobiotics and food components interact with hepatic transporters assists in predicting adverse drug reactions. This assay helps in identifying potential inhibitors that could alter bile acid homeostasis and subsequent liver function.

Highlights of Our Service

• Innovative Fluorescence-Based Approach
• Compliance and Quality
• Expertise and Technological Prowess

Frequently Asked Questions

Q1: Why is BSEP inhibition a concern in drug development?

A1: The inhibition of BSEP can lead to the accumulation of bile acids within hepatocytes, resulting in cholestasis and potentially severe DILI. Understanding a drug's interaction with BSEP is essential to mitigate these risks and ensure liver safety.

Q2: What are the advantages of using a fluorescence-based assay?

A2: Fluorescence-based assays are cost-effective, sensitive, and safe, offering an efficient alternative to radiolabeled methodologies. They allow for high-throughput screening and provide reliable quantification suitable for both early-stage and regulatory studies.

At Creative Biolabs, we are committed to advancing the field of drug transporter studies. Our Human Transporter BSEP Fluorescence-based inhibition Assay Service is at the forefront of innovation, providing the pharmaceutical industry with reliable tools for safer and more effective drug development.

References

1. Liu, Hongtao, et al. "Structural basis of bile salt extrusion and small-molecule inhibition in human BSEP." Nature Communications 14.1 (2023): 7296.
2. Distributed under Open Access License CC BY 4.0, without modification.

For Research Use Only | Not For Clinical Use