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• W2062786215 abstract "Recent studies have demonstrated that a member of the nuclear receptor family, pregnane X receptor (PXR) is a key regulator of the expression of cytochrome P450 3A (CYP3A) in humans and rodents. It is also known that species specificity in the induction of CYP3A by xenobiotics is likely a consequence of differences at the level of PXR activation. Because of the importance of CYP3A4 in drug metabolism, the development of rapid and accurate in vitro assays for predicting the effects of compounds on CYP3A4 expression or activity in humans has been a long-standing goal within pharmaceutical industries. PXR activation measurements using an in vitro reporter gene approach appears to provide a rapid and relatively inexpensive means for predicting whether compounds will induce CYP3A levels in vivo. In this study, using an HepG2 cell based human and mouse PXR reporter gene assay, 23 compounds were tested for their potential to activate hPXR or mPXR. Data demonstrated that potent activators of hPXR had virtually no activity on mPXR and efficient activators of mPXR had weak activity on hPXR. In addition, a third category of moderate/weak activators of both hPXR and mPXR was identified. Exemestane was a strong activator of mPXR (∼22-fold activation) with only minor effect on hPXR (∼5-fold activation). The importance of cell viability measurements as part of the PXR reporter gene assay was demonstrated as significant cytotoxicity or inhibition of cell proliferation might underestimate the potential for PXR activation." @default.
• W2062786215 created "2016-06-24" @default.
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• W2062786215 date "2004-06-01" @default.
• W2062786215 modified "2023-10-18" @default.
• W2062786215 title "A human and mouse pregnane X receptor reporter gene assay in combination with cytotoxicity measurements as a tool to evaluate species-specific CYP3A induction" @default.
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• W2062786215 doi "https://doi.org/10.1016/j.tox.2003.12.018" @default.
• W2062786215 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/15125996" @default.
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