Cytochrome P450 enzymes (CYPs) are integral to drug metabolism and implicated in the biotransformation of approximately 80% of all administered drugs. Of these, CYP2C19 is particularly significant due to its role in metabolizing various clinically relevant drugs, including proton pump inhibitors, antiepileptics, and antidepressants. Drug-drug interactions (DDIs) resulting from CYP2C19 inhibition can lead to adverse drug reactions (ADRs) and therapeutic failures. Therefore, determining the inhibition potential, represented as the IC50 value, is crucial for predicting possible DDIs and for the safe co-administration of drugs.

Our CYP2C19 Inhibition IC50 Assessment Service

At Creative Biolabs, we offer a state-of-the-art CYP2C19 Inhibition IC50 Assessment Service that utilizes cutting-edge technology to provide accurate and reliable data. Our service encompasses comprehensive assay development, sophisticated data analysis, and detailed reporting, which collectively enable our clients to de-risk their drug development processes effectively.

Services Information

• Assay Development and Execution

Our service employs a detailed enzymatic assay explicitly tailored for CYP2C19. The assay involves pre-incubating the substrate (0.5 µM Omeprazole) with microsomal preparations for five minutes, followed by a 10-minute incubation with NADPH at 37°C. The inhibition is measured by the reduction in metabolite formation, allowing precise IC50 calculation.

• Test Sample Requirements

Minimum for Screening: 100 µl of 10 mM stock or 1 to 2 mg (pre-weighed).

Dose Response: 250 µl of 10 mM stock or 1.5 to 2 mg (pre-weighed).

• Automated High-Throughput Screening

Our high-throughput screening platform can evaluate up to 77 test compounds along with 11 control inhibitors for multiple CYP enzymes simultaneously. Using human liver microsomes (HLMs) and cDNA-expressed recombinant CYPs, we ensure an accurate reflection of in vivo conditions. We use liquid chromatography-tandem mass spectrometry (LC-MS/MS) for rapid sample analysis, reducing turnaround times significantly.

• Statistical Modeling for IC50 Prediction

Leveraging a robust statistical model, we predict IC50 values from single inhibitor concentration data points, optimizing assay throughput and resource efficiency. This model, applicable across various CYPs and microsomal systems, enables reliable IC50 value estimation with a 95% confidence interval, enhancing the screening capacity without compromising accuracy.

• Time-Dependent and Mechanism-Based Inhibition

We provide specialized assays to determine time-dependent inhibition (TDI) and mechanism-based inactivation (MBI) of CYP2C19 by incorporating pre-incubation steps with and without NADPH. These assays help elucidate the persistence and potential clinical impact of enzyme inhibition by test compounds.

Application Prospect

Features & Benefits

Scientific Data

Representative Data from H. helix Extract Study

The IC50 values for H. helix extracts against CYP2C19 obtained using human liver microsomes and recombinant enzymes were 1.04 ± 0.06 mg/mL and 0.58 ± 0.03 mg/mL, respectively. The time-dependent shift in IC50 values further confirmed the extract's potential to cause time-dependent inhibition of CYP2C19.

Fig.1 Effects of hederacoside C on the CYP-specific metabolite formation in human liver microsomes.^1,2

Frequently Asked Questions

Q1: How long does the CYP2C19 inhibition IC50 assessment take?

A1: The typical turnaround time for our IC50 assessment, including TDI and MBI testing, is under two weeks, depending on the assay complexity and sample volume.

Q2: What sample quantities are needed for the IC50 assessment service?

A2: For screening, a minimum of 100 µl of a 10 mM stock or 1 to 2 mg of pre-weighed compound is required. For dose-response assays, 250 µl of a 10 mM stock or 1.5 to 2 mg (pre-weighed) is necessary.

Q3: Can this service be used for herbal extracts?

A3: Yes, our service evaluates a wide range of substances, including herbal extracts, as demonstrated by our study on Hedera helix. We assess their inhibition potential on CYP enzymes to predict possible herb-drug interactions.

At Creative Biolabs, our advanced CYP2C19 Inhibition IC50 Assessment Service stands as a cornerstone for accurate prediction and evaluation of drug-drug interactions. Our comprehensive assays, coupled with high-throughput capabilities and rigorous data analysis, provide indispensable insights for safer and more effective drug development.

References

1. Rehman, Shaheed Ur, et al. "Time-dependent Inhibition of CYP2C8 and CYP2C19 by Hedera helix extracts, a traditional respiratory herbal medicine." Molecules 22.7 (2017): 1241.
2. under Open Access License CC BY 4.0, without modification.

For Research Use Only | Not For Clinical Use