Chemical genomics is the name we have given to the analysis of gene function through use of small molecule chemical tools. Orphan nuclear receptors are ideally suited to this technique of functional analysis, since their activity as transcription factors is regulated by small hydrophobic ligands. GW4064 is a potent and selective nonsteroidal ligand for the nuclear bile acid receptor FXR (NR1H4). Using GW4064 as a chemical tool, we have identified genes regulated by FXR in the liver, including those involved in bile acid synthesis and transport. We have also discovered that PXR (NR1I2) is a lithocholic acid receptor that controls the biosynthesis and metabolism of bile acids. Together FXR and PXR cooperate to control biliary and urinary bile acid excretion. These functions suggest that potent PXR and FXR ligands may offer a new approach to the treatment of cholestatic liver disease.

中文翻译：

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化学基因组学：孤儿核受体在胆汁酸代谢调节中的功能分析。

化学基因组学是我们通过使用小分子化学工具来分析基因功能的名称。孤儿核受体非常适合这种功能分析技术，因为它们作为转录因子的活性受小的疏水性配体的调节。GW4064是核胆汁酸受体FXR（NR1H4）的有效且选择性的非甾体配体。使用GW4064作为化学工具，我们在肝脏中鉴定了受FXR调控的基因，包括参与胆汁酸合成和运输的基因。我们还发现，PXR（NR1I2）是控制胆汁酸生物合成和代谢的胆石酸受体。FXR和PXR共同控制胆汁和尿液胆汁酸的排泄。