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Correlation of High-Throughput Pregnane X Receptor (PXR) Transactivation and Binding Assays

2004; Elsevier BV; Volume: 9; Issue: 6 Linguagem: Inglês

10.1177/1087057104264902

2472-5560

Zhengrong Zhu, Sean Kim, Taosheng Chen, Jun-Hsiang Lin, Aneka Bell, James Bryson, Yves Dubaquié, Ning Yan, Joseph Yanchunas, Dianlin Xie, Robert H. Stoffel, Michael Sinz, Kenneth E.J. Dickinson,

Hormonal and reproductive studies

Pregnane X receptor (PXR) transactivation and binding assays have been developed into high-throughput assays, which are robust and reproducible (Z' > 0.5). For most compounds, there was a good correlation between the results of the transactivation and binding assays. EC(50) values of compounds in the transactivation assay correlated reasonably well with their IC(50) values in the binding assay. However, there were discrepancies with some compounds showing high binding affinity in the binding assay translated into low transactivation. The most likely cause for these discrepancies was an agonist-dependent relationship between binding affinity and transactivation response. In general, compounds that bound to human PXR and transactivated PXR tended to be large hydrophobic molecules.