PXR reporter gene assays

R. (2004) A PXR reporter gene assay in a stable cell culture system CYP3A4 and CYP2B6 induction by pesticides. Biochemical Pharmacology, 68,2347-2358. 

Variations of the PXR reporter gene assay have been developed in a number of laboratories. In our laboratory, DNA vectors were constructed... 

TABLE 17.2 Summary of Human PXR reporter gene assays used in several laboratories. 

As mentioned above, all the methods currently employed for measuring CYP3A4 induction, including humanized mice, PXR reporter gene assays, and primary cultures of human hepatocytes, have limitations. Most importantly. 

CYP induction may cause opposite effects of CYP inhibition in that the exposure of the drug may be reduced. In rodents, the major induction issue appears to be the induction of the CYP lA, CYP 2B, and CYP 3A family. There are considerably literatures suggesting that nuclear receptors, such as AhR, CAR and PXR, are involved in the induction of the respective CYPs [30]. In humans, the major induction pathway appears to be controlled by PXR. Administration of PXR agonists, such as rifampicin, causes elevated levels of intestinal and hepatic CYP 3A4, resulting in the reduction of oral bioavailability. CYP induction potential can be measured by certain in vitro assays, such as PXR-reporter gene assay and hepato-cyte induction assay [4, 31]. 

PXR Binding Reporter Gene Assays Scaled Down Heptocyte Induction Heptocyte Induction EC50/Emax (N=3)... 

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