Pregnane X receptor ligands

Ekins S, Erickson JA. A pharmacophore for human pregnane X-receptor ligands. Drug Metab Dispos 2002 30 96-9. 

B., Goodwin, B., Liddle, C. Blanchard, S. G., Willson, T.M., Collins, J.L. and Kliewer, S.A (2000) Orphan nuclear receptors constitutive androstane receptor and pregnane X receptor share xenobiotic and steroid ligands. The Journal of Biological Chemistry, 275, 15122-15127. 

Kobayashi, K., Yamagami, S., Higuchi, T., Hosokawa, M. and Chiba, K. (2004) Key structural features of ligands for activation of human pregnane X receptor. Drug Metabolism and Disposition The Biological Fate of Chemicals, 32, 468-472. 

H. Masuyama, N. Suwaki, Y. Tateishi, H. Nakatsukasa, T. Segawa, and Y. Hiramatsu. The pregnane X receptor regulates gene expression in a ligand- and promoter-selective fashion. Mol Endocrinol. 19 1170-1180 (2005). 

Recently, Geick et al. [79] discovered a complex regulatory cluster of several binding sites for the ligand-activated nuclear receptor, pregnane X receptor... 

Figure 9.10 Illustration depicting DNA elements found in CYP3A genes and the activation of the human pregnane X receptor (PXR) by ligand (RIF) and subsequent transcriptional activation of CYP3A4 gene by the PXR/RXR heterodimer. dNR-1-3, nuclear receptors 1, 2, and 3, respectively PXR, pregnane X receptor RXR, retinoid X receptor RIF, rifampicin SRC-1, steroid receptor co-activator XREM, xenobiotic responsive enhancer module.

Table 2 Nuclear receptors (NR) for enzyme inducers. Enzyme inducers are now known to act as ligands to nuclear receptors, leading to gene activation and increased synthesis of the enzyme. Affinity of inducers to die receptors is now known to be responsible for the differential induction potential and can explain die observed species-differences in induction. The receptors tabulated are aryl hydrocarbon receptors (AhR), constituitively androstane receptor (CAR), pregnane X receptor (PXR), and glucocorticoid receptor (GR). The isoforms in bold type are the major isoform regulated by the corresponding receptors.

Watkins RE, Davis-Searles PR, Lambert MH, Redinbo MR. Coactivator binding promotes the specific interaction between ligand and the pregnane X receptor. J Mol Biol 2003 331 815-28. 

Dussault I, Yoo HD, Lin M, Wang E, Lan M, Batta AK, et al. Identification of an endogenous ligand that activates pregnane X receptor-mediated sterol clearance. Proc Natl Acad Sci USA 2003 100 833-8. 

Squires EJ, Sueyoshi T, Negishi M (2004) Cytoplasmic localization of pregnane X receptor and ligand-dependent nuclear translocation in mouse liver. J Biol Chem 279(47) 49307 9314. doi 10.1074/jbc. M407281200... 

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