CYP2C9 induction (human hepatocytes, mRNA level, 3 donors) - US

Background Information:

Cytochrome P450 (CYP) enzymes can be induced by many xenobiotics (chemical inducers) including some drugs through the mediation of nuclear receptors. Three major nuclear receptors that mediate CYP induction are Aryl hydrocarbon receptor (AhR) for CYP1A2, constitutive androstane receptor (CAR) for CYP2B6, and pregnane X receptor (PXR) for CYP3A4 and CYP2C. Activated nuclear receptor will increase mRNA level through transcriptional activation of genes for the corresponding CYP isoforms and subsequently increase expression of these isoforms. Pharmacokinetic profile of a drug can be substantially altered by induced CYP isozymes. To minimize the drug interaction liability, understanding CYP induction potential of a new molecular entity (NME) is critical. Eurofins Panlabs has developed robust CYP induction assays using mRNA as the end point to evaluate CYP induction potential of NME. It is recommended that the induction of CYP1A2, CYP2B6 and CYP3A4 by a NME is evaluated first. Since both CYP3A4 and CYP2C isozymes are regulated by the same nuclear receptor (PXR), it is essential to assess CYP2C induction if a NME induces CYP3A4. The potential of a NME to induce CYP2C8, CYP2C9 and CYP2C19 is determined by measuring the mRNA level of those isozymes from human primary hepatocytes from 3 donors.

Family:

CYP450

Sub Family:

CYP3

Organism:

Human

Construct Details:

Endogenous

Cell Type:

Hepatocytes