What is a CYP assay?

Cytochrome P450 (CYP) are a family of enzymes which play a major role in the metabolism of drugs. In Cyprotex’s Cytochrome P450 Inhibition assay, a decrease in the formation of the metabolites compared to the vehicle control is used to calculate an IC50 value (test compound concentration which produces 50% inhibition).

Why are CYP450 assays performed?

Cytochrome P450 (P450) enzymes are important in the metabolism of steroids, vitamins, carcinogens, drugs and other compounds. Two of the commonly used assays in this field are the measurements of total P450 and NADPH–P450 reductase in biological preparations. Each assay can be completed in 5–10 min.

What is CYP induction assay?

The cytochrome P450 (CYP450) induction assay provides a means to assess whether or not a test compound increases the production of specific CYP450 enzymes. Understanding the potential for CYP induction by a new chemical entity (NCE) is important to minimize adverse drug-drug interactions.

What is the purpose of CYP?

Background: The cytochrome P450 (CYP) enzymes are membrane-bound hemoproteins that play a pivotal role in the detoxification of xenobiotics, cellular metabolism and homeostasis. Induction or inhibition of CYP enzymes is a major mechanism that underlies drug-drug interactions.

How CYP enzymes are induced?

The most common mechanism of CYP enzyme induction is transcriptional gene activation. Nuclear receptors, such as the aryl hydrocarbon receptor (AhR), pregnane X receptor (PXR) and constitutive androstane receptor (CAR), mediate drug-induced changes in the expression of phase I and phase II enzymes and transporters.

What does CYP450 inhibition mean?

Reversible inhibition
CYP450 inhibitors are used to minimize or prevent such reactions. Drugs are metabolized in many sites of our body; however, the liver is the primary organ for drug metabolism. CYP450 inhibition can be categorized as: Reversible inhibition (a result of rapid association and dissociation between drugs and CYP enzymes)

What is CYP inhibition assay?

CYP Inhibition assays are typically performed with pooled human liver microsomes from 200 donors (XTreme 200). This allows the same sample of pooled human liver microsomes and similar experimental conditions to be used to study all CYP enzymes of interest.

How do CYP inducers work?

Enzyme Induction CYP enzyme inducers increase the rate of hepatic metabolism, usually through increased transcription of mRNA, and decrease serum concentrations of other drugs metabolized by the same hepatic isoenzyme.

What does a CYP inhibitor do?

CYP450 inhibitors are used to minimize or prevent such reactions. Drugs are metabolized in many sites of our body; however, the liver is the primary organ for drug metabolism.

Which is CYP P450 inhibitor?

Significant Cytochrome P450 Enzymes and Their Inhibitors, Inducers, and Substrates

How do CYP450 inhibitors work?

Thus, the mechanism of CYP enzymes is often referred to as “A double-edged sword”. CYP450 inhibition can be categorized as: Reversible inhibition (a result of rapid association and dissociation between drugs and CYP enzymes) Irreversible inhibition (a long-lasting loss of enzyme activity)

What does Cyprotex cytochrome P450 inhibition assay do?

Cyprotex deliver consistent, high quality data with cost-efficiency that comes from a highly automated approach. Cytochrome P450 (CYP) are a family of enzymes which play a major role in the metabolism of drugs.

How is the rhcyp fluorescent assay used in drug discovery?

The rhCYP-fluorescent assay is high throughput (100–1000 compounds/day) and is often used at the early stages of drug discovery to assess potential CYP450 inhibition liabilities of thousands of compounds.

How are enzyme activity levels used in CYP induction?

Enzyme activity levels using a specific probe substrate may also be used to quantify CYP induction; however, the challenge of this approach is the possible masking of a positive induction result when concurrent inhibition occurs.

How to determine potential induction of cytochrome P450 ( CYP450 )?

Determining potential induction of cytochrome P450 (CYP450) enzymes 1 Induction of cytochrome P450 enzymes is associated with an increased prevalence… 2 Cyprotex’s Cytochrome P450 induction assay identifies the potential of test compounds… 3 Test drug concentrations should be based on the expected human plasma drug concentrations and dose.