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- W2757088049 abstract "Many drugs bind to and activate human pregnane X receptor (hPXR) to upregulate drug-metabolizing enzymes, resulting in decreased drug efficacy and increased resistance. This suggests that hPXR antagonists have therapeutic value. Here we report that SPA70 is a potent and selective hPXR antagonist. SPA70 inhibits hPXR in human hepatocytes and humanized mouse models and enhances the chemosensitivity of cancer cells, consistent with the role of hPXR in drug resistance. Unexpectedly, SJB7, a close analog of SPA70, is an hPXR agonist. X-ray crystallography reveals that SJB7 resides in the ligand-binding domain (LBD) of hPXR, interacting with the AF-2 helix to stabilize the LBD for coactivator binding. Differential hydrogen/deuterium exchange analysis demonstrates that SPA70 and SJB7 interact with the hPXR LBD. Docking studies suggest that the lack of the para-methoxy group in SPA70 compromises its interaction with the AF-2, thus explaining its antagonism. SPA70 is an hPXR antagonist and promising therapeutic tool.The xenobiotic-activated human pregnane X receptor (hPXR) regulates drug metabolism. Here the authors develop hPXR modulators, which are of potential therapeutic interest and functionally and structurally characterize the antagonist SPA70 and the structurally related agonist SJB7." @default.
- W2757088049 created "2017-10-06" @default.
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- W2757088049 date "2017-09-29" @default.
- W2757088049 modified "2023-10-12" @default.
- W2757088049 title "SPA70 is a potent antagonist of human pregnane X receptor" @default.
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- W2757088049 cites W1984615841 @default.
- W2757088049 cites W1988423359 @default.
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- W2757088049 cites W2028910937 @default.
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- W2757088049 doi "https://doi.org/10.1038/s41467-017-00780-5" @default.
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