Cytochrome P450 Assay
Creative Animodel is an expert provider in the frontier of DMPK and has conducted many Cytochrome P450-related studies. We have state-of-the-art facilities managed by experienced staff. Our high-quality services and reliable results make it possible to meet various demands from the early stage of drug discovery to the new drug declaration.
What Is Cytochrome P450 in Drug Metabolism?
Cytochromes P450 (CYP450 or CYPs) are hemoproteins which constitute a superfamily containing heme as a cofactor. The human cytochrome P450 system is implicated in many drug interactions. CYP450 are the major enzymes involved in drug metabolism, accounting for about 75% of the total metabolism. Drug metabolism related CYP450 in human liver microsomes are mainly classified into five categories (Figure1), including CYP1A, CYP2C, CYP2D, CYP2E and CYP3A. And it is important to investigate which one of the main CYP450 isoforms is essentially involved in the in vitro metabolism of a drug. Many drugs may increase or decrease the activity of CYP450 either by inducing the biosynthesis of an isozyme or by inhibiting the activity of CYP450. Drugs that cause CYP450 drug interactions are referred to as either inhibitors or inducers.
Figure 1. The major CYP450s participating in drug metabolism in human liver microsomes
Cytochrome P450 Services
Cytochrome P450 Reaction Phenotyping Assay
Cytochrome P450 reaction phenotyping assay uses expressed enzymes to identify which drug metabolizing isoforms are responsible for the metabolism of a test compound. As CYP450 can exhibit polymorphisms which can affect plasma levels in vivo, it is important to identify whether it is expected to be a problem at an early stage of drug development.
Cytochrome P450 Induction Assay
A compound that induces CYP450 enzymes may alter the metabolism of other drugs, resulting in a loss of efficacy of that drug. Assaying time independent inhibition of drugs in vitro plays an important role in drug development. We conduct the CYP450 induction assay by assessing mRNA levels and catalytic activity in cultured human hepatocytes to identify the potential of the compounds to induce some CYP450.
Cytochrome P450 Inhibition Assay
It is essential to assess the potential possibility whether a compound inhibits a specific cytochrome P450 enzyme as co-administration of compounds. This may affect plasma levels in vivo and possibly lead to adverse drug reactions or toxicity. In the CYP450s inhibition assay, a decrease in the formation of the metabolites compared to the vehicle control is used to calculate an IC50 value (i.e. test compound concentration which produces 50% inhibition) by LC-MS/MS.
Cytochrome P450 Time Dependent Inhibition Assay
Time dependent inhibition of cytochrome P450 can lead to clinically relevant drug-drug interactions or non-linear pharmacokinetics of a drug. We provide different methods for CYP450 time dependent inhibition assay, including single point assay, IC50 shift assay and Kinact/KI assay.
• All assays are designed to meet FDA and EMA requirement.
• Based on state-of-the-art equipment, delivery of data within a short time to speed up process.
• Various methods to meet different demands, such as liver microsomes or recombinant CYP enzymes.
Creative Animodel has professional experts to help you design the best strategies for the whole process of drug discovery and development. Moreover, if you have any other needs, we would love to design studies to address clients’ specific requirements. We are confident to provide high-quality data for our clients to facilitate their researches.