CYP3A4 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. Hepatocytes from 3 lots are assessed by a set of known positive and negative inducers to establish a cutoff value of induction for CYP1A2, CYP2B6 and CYP3A4. The hepatocytes from the same 3 lots are used to screen test compounds. The potential of a test compound to induce CYP isozymes is determined by comparison of the fold induction with the pre-determined cut-off values.

Family:

CYP450

Sub Family:

CYP3

Protein Name:

CYP3A4

Uniprot Number:

P08684

Gene Name:

CYP3A4

Gene ID:

1576

Organism:

Human

Construct Details:

Endogenous

Cell Type:

Hepatocytes