Introduction

Organic Anion Transporting Polypeptide 1B1 (OATP1B1) is a crucial transporter protein predominantly expressed in human hepatocytes. This transporter plays a significant role in the hepatic uptake of a wide range of drugs and endogenous compounds, including statins, bile acids, and bilirubin. Notably, OATP1B1's function and its interaction with various substrates and inhibitors are pivotal for understanding drug-drug interactions (DDIs) and the pharmacokinetic profiles of therapeutic compounds.

Inhibition of OATP1B1 can lead to increased systemic exposure to drugs, particularly statins, with potential adverse effects such as myopathy and rhabdomyolysis. Therefore, assessing the inhibitory potential (IC50) of compounds on OATP1B1 is essential for drug development and safety evaluations. Creative Biolabs provides a comprehensive Human Transporter OATP1B1 Inhibition IC50 Assessment Service designed to deliver accurate and reliable data for your specific needs.

Human Transporter OATP1B1 Inhibition IC50 Assessment Service at Creative Biolabs

With state-of-the-art technology and scientific expertise, Creative Biolabs offers an advanced Human Transporter OATP1B1 Inhibition IC50 Assessment Service. Our service integrates cell-based assays, high-throughput screening, and sophisticated analytical methods to determine the IC50 values of test compounds. By using our service, clients can ensure their compounds' potential interactions with OATP1B1 are thoroughly examined, thus contributing to safer and more effective drug development.

Service Details

• Cell-Based Assays

Our service employs stable cell lines expressing OATP1B1 to facilitate accurate and reproducible measurement of drug uptake and inhibition using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Assay Procedure

• High-Throughput Screening

The high-throughput nature of our assay allows for the screening of extensive chemical libraries, identifying both known and novel inhibitors. This capability is essential for large-scale drug discovery projects where multiple compounds need to be screened in a cost-effective and time-efficient manner.

Features of Our Service

• Precision and Accuracy

Our service guarantees high precision and accuracy in IC50 determination, with a focus on minimizing variability and ensuring reproducible results.

• Use of Physiologically Relevant Models

By using primary human hepatocytes and sandwich-cultured hepatocyte models, we ensure that the inhibitory effects observed are relevant to human physiology, enhancing the translational value of our data.

• Comprehensive Data Output

Clients receive detailed reports including raw data, IC50 calculations, and comprehensive analyses comparing different compounds and control inhibitors. This thorough output enables informed decision-making in further drug development stages.

• Advanced Analytical Techniques

We employ liquid chromatography-tandem mass spectrometry (LC-MS/MS) for highly sensitive and specific detection of test compounds and substrates, ensuring the robustness of our assay results.

Scientific Backing

Studies have shown the critical roles of OATP1B1 in hepatic drug uptake and the implications for drug safety and efficacy. For instance, the article explores the mechanisms of trans-inhibition of OATP1B1 and OATP1B3 by calcineurin inhibitors (CNIs) like cyclosporine A (CsA) and tacrolimus, comparing their effects with a non-immunosuppressive analog SCY-635. The study identifies several proteins associated with OATP1B1/3 regulation, suggesting calcineurin inhibition is not solely responsible for trans-inhibition, implicating additional regulatory mechanisms involving kinase modulation and ubiquitination.

Fig.1 Effects of tacrolimus pre-incubation on OATP1B1 and OATP1B3 transporter expression cell lines.^1,2

Frequently Asked Questions

Q1: What substrates do you commonly use for OATP1B1 inhibition assays?

A1: We primarily use fluorescein-methotrexate (FMTX) due to its optimal signal and transport efficiency. Alternative substrates may be employed based on specific requirements.

Q2: How do you ensure the reliability of the IC50 values obtained?

A2: We validate our assays using known inhibitors and compare IC50 values derived from multiple substrates. Additionally, high reproducibility and low variability in our assays further ensure reliability.

Q3: Can you handle high-throughput screening for large chemical libraries?

A3: Yes, our assay is designed for high-throughput screening, allowing us to efficiently process large chemical libraries and identify potential inhibitors accurately and quickly.

Integrating sophisticated assay techniques, preincubation protocols, high-throughput platforms, and proteomic analyses, Creative Biolabs' Human Transporter OATP1B1 Inhibition IC50 Assessment Service stands out as a premier choice for comprehensive drug interaction studies. This service not only offers precise IC50 values but also digs deeper into the mechanistic aspects of transporter inhibition, ensuring that your drug candidates are evaluated with the highest standards of scientific rigor.

References

1. Powell, John T., et al. "Assessing Trans-Inhibition of OATP1B1 and OATP1B3 by Calcineurin and/or PPIase Inhibitors and Global Identification of OATP1B1/3-Associated Proteins." Pharmaceutics 16.1 (2023): 63.
2. Distributed under Open Access License CC BY 4.0, without modification.

For Research Use Only | Not For Clinical Use