{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNR1I2, also known as the pregnane X receptor (PXR), is a ligand‐activated nuclear receptor that functions as a master xenobiotic sensor. By binding a remarkably wide spectrum of structurally diverse compounds—including synthetic drugs such as rifampicin and paclitaxel, as well as dietary and endogenous molecules—NR1I2 orchestrates the transcriptional regulation of key drug‐metabolizing enzymes (for example, CYP3A4, CYP2C8, CYP2B6) and transporters like P‐glycoprotein. Structural studies have revealed a highly plastic ligand–binding domain that facilitates differential recruitment of coactivators and corepressors, thereby explaining species‐specific activation patterns and providing a molecular basis for many clinically significant drug–drug interactions and metabolic adaptations."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its fundamental role in xenobiotic detoxification, NR1I2 exerts significant influence over endogenous metabolic pathways. It modulates lipid homeostasis by inducing the expression of fatty acid transporters and lipogenic enzymes, contributing to hepatic triglyceride accumulation, and it plays an important part in regulating bile acid and cholesterol metabolism—processes that are critically interwoven with vitamin D catabolism. Furthermore, NR1I2 activation by compounds such as vitamin K₂ has been shown to drive osteoblastic marker expression and bolster bone formation. This extensive metabolic crosstalk, which also involves interactions with other transcription factors and nuclear receptors (thereby impacting gluconeogenesis and immune/inflammatory signaling), underscores NR1I2’s pivotal role in maintaining overall physiological and endocrine homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "24"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic polymorphisms, alternative transcript variants, and post‐transcriptional regulatory mechanisms further contribute to interindividual differences in NR1I2 function, influencing drug disposition and toxicity. For instance, microRNAs such as miR-148a modulate NR1I2 translational efficiency, while different splice isoforms display variable capability to upregulate phase II enzymes. Clinical pharmacogenomic studies have linked NR1I2 variants to altered responses to therapies—including tamoxifen, tacrolimus, and docetaxel—and have implicated the receptor in the progression of malignancies such as colon and lung cancer. Moreover, NR1I2’s tissue‐specific expression patterns, its regulated nuclear translocation, and its interactions with coregulatory proteins underlie its diverse roles in controlling inflammatory responses, maintaining intestinal barrier function, and modulating other signal transduction pathways. Collectively, these insights highlight the therapeutic potential of targeting NR1I2 to optimize drug efficacy and minimize adverse effects."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "25", "end_ref": "43"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "J M Lehmann, D D McKee, M A Watson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (1998)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI3703"}], "href": "https://doi.org/10.1172/JCI3703"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "9727070"}], "href": "https://pubmed.ncbi.nlm.nih.gov/9727070"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Changcheng Zhou, Michelle M Tabb, Edward L Nelson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutual repression between steroid and xenobiotic receptor and NF-kappaB signaling pathways links xenobiotic metabolism and inflammation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI26283"}], "href": "https://doi.org/10.1172/JCI26283"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16841097"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16841097"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Mia Wadelius, Leslie Y Chen, Niclas Eriksson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of warfarin dose with genes involved in its action and metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Genet (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00439-006-0260-8"}], "href": "https://doi.org/10.1007/s00439-006-0260-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17048007"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17048007"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Wen Xie, Mei-Fei Yeuh, Anna Radominska-Pandya, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Control of steroid, heme, and carcinogen metabolism by nuclear pregnane X receptor and constitutive androstane receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0438010100"}], "href": "https://doi.org/10.1073/pnas.0438010100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12644700"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12644700"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Xinsheng Gu, Sui Ke, Duan Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of NF-kappaB in regulation of PXR-mediated gene expression: a mechanism for the suppression of cytochrome P-450 3A4 by proinflammatory agents."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M601302200"}], "href": "https://doi.org/10.1074/jbc.M601302200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16608838"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16608838"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ryan E Watkins, Paula R Davis-Searles, Mill H Lambert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Coactivator binding promotes the specific interaction between ligand and the pregnane X receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0022-2836(03)00795-2"}], "href": "https://doi.org/10.1016/s0022-2836(03"}, {"type": "t", "text": "00795-2) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12909012"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12909012"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Sonali Bhalla, Cengiz Ozalp, Sungsoon Fang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ligand-activated pregnane X receptor interferes with HNF-4 signaling by targeting a common coactivator PGC-1alpha. Functional implications in hepatic cholesterol and glucose metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M405423200"}], "href": "https://doi.org/10.1074/jbc.M405423200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15322103"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15322103"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Björn Bauer, Xiaodong Yang, Anika M S Hartz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "In vivo activation of human pregnane X receptor tightens the blood-brain barrier to methadone through P-glycoprotein up-regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Pharmacol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/mol.106.023796"}], "href": "https://doi.org/10.1124/mol.106.023796"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16837625"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16837625"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Oliver Burk, Ina Koch, Judy Raucy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The induction of cytochrome P450 3A5 (CYP3A5) in the human liver and intestine is mediated by the xenobiotic sensors pregnane X receptor (PXR) and constitutively activated receptor (CAR)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M404949200"}], "href": "https://doi.org/10.1074/jbc.M404949200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15252010"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15252010"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Stephanie R Faucette, Hongbing Wang, Geraldine A Hamilton, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of CYP2B6 in primary human hepatocytes by prototypical inducers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Drug Metab Dispos (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/dmd.32.3.348"}], "href": "https://doi.org/10.1124/dmd.32.3.348"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14977870"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14977870"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Changcheng Zhou, Emma-Jane Poulton, Felix Grün, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The dietary isothiocyanate sulforaphane is an antagonist of the human steroid and xenobiotic nuclear receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Pharmacol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/mol.106.029264"}], "href": "https://doi.org/10.1124/mol.106.029264"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17028159"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17028159"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Sean Ekins, Cheng Chang, Sridhar Mani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human pregnane X receptor antagonists and agonists define molecular requirements for different binding sites."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Pharmacol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/mol.107.038398"}], "href": "https://doi.org/10.1124/mol.107.038398"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17576789"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17576789"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Tomas Smutny, Sridhar Mani, Petr Pavek "}, {"type": "b", "children": [{"type": "t", "text": "Post-translational and post-transcriptional modifications of pregnane X receptor (PXR) in regulation of the cytochrome P450 superfamily."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Drug Metab (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2174/1389200214666131211153307"}], "href": "https://doi.org/10.2174/1389200214666131211153307"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24329114"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24329114"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Yu Xue, Linda B Moore, Jillian Orans, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Crystal structure of the pregnane X receptor-estradiol complex provides insights into endobiotic recognition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Endocrinol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/me.2006-0323"}], "href": "https://doi.org/10.1210/me.2006-0323"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17327420"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17327420"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Vishal Lamba, John C Panetta, Stephen Strom, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic predictors of interindividual variability in hepatic CYP3A4 expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Pharmacol Exp Ther (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/jpet.109.160804"}], "href": "https://doi.org/10.1124/jpet.109.160804"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19934400"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19934400"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Jie Zhou, Yonggong Zhai, Ying Mu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel pregnane X receptor-mediated and sterol regulatory element-binding protein-independent lipogenic pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M511116200"}], "href": "https://doi.org/10.1074/jbc.M511116200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16556603"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16556603"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Michelle M Tabb, Aixu Sun, Changcheng Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Vitamin K2 regulation of bone homeostasis is mediated by the steroid and xenobiotic receptor SXR."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M303136200"}], "href": "https://doi.org/10.1074/jbc.M303136200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12920130"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12920130"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Jean Marc Pascussi, Agnes Robert, Minh Nguyen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Possible involvement of pregnane X receptor-enhanced CYP24 expression in drug-induced osteomalacia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI21867"}], "href": "https://doi.org/10.1172/JCI21867"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15630458"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15630458"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Changcheng Zhou, Mahfoud Assem, Jessica C Tay, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Steroid and xenobiotic receptor and vitamin D receptor crosstalk mediates CYP24 expression and drug-induced osteomalacia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI27793"}], "href": "https://doi.org/10.1172/JCI27793"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16691293"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16691293"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Tomoe Ichikawa, Kuniko Horie-Inoue, Kazuhiro Ikeda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Steroid and xenobiotic receptor SXR mediates vitamin K2-activated transcription of extracellular matrix-related genes and collagen accumulation in osteoblastic cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M600896200"}], "href": "https://doi.org/10.1074/jbc.M600896200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16606623"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16606623"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Stephen S Ferguson, Yuping Chen, Edward L LeCluyse, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human CYP2C8 is transcriptionally regulated by the nuclear receptors constitutive androstane receptor, pregnane X receptor, glucocorticoid receptor, and hepatic nuclear factor 4alpha."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Pharmacol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/mol.105.013169"}], "href": "https://doi.org/10.1124/mol.105.013169"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15933212"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15933212"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Megan M Dring, Carol A Goulding, Valerie I Trimble, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The pregnane X receptor locus is associated with susceptibility to inflammatory bowel disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gastroenterology (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1053/j.gastro.2005.12.008"}], "href": "https://doi.org/10.1053/j.gastro.2005.12.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16472590"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16472590"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Yoshihiro Konno, Masahiko Negishi, Susumu Kodama "}, {"type": "b", "children": [{"type": "t", "text": "The roles of nuclear receptors CAR and PXR in hepatic energy metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Drug Metab Pharmacokinet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2133/dmpk.23.8"}], "href": "https://doi.org/10.2133/dmpk.23.8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18305370"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18305370"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Susumu Kodama, Rick Moore, Yukio Yamamoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human nuclear pregnane X receptor cross-talk with CREB to repress cAMP activation of the glucose-6-phosphatase gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20070481"}], "href": "https://doi.org/10.1042/BJ20070481"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17635106"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17635106"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Shingo Takagi, Miki Nakajima, Takuya Mohri, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Post-transcriptional regulation of human pregnane X receptor by micro-RNA affects the expression of cytochrome P450 3A4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M709382200"}], "href": "https://doi.org/10.1074/jbc.M709382200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18268015"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18268015"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Mónica B Frungieri, Stephan Weidinger, Viktor Meineke, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Proliferative action of mast-cell tryptase is mediated by PAR2, COX2, prostaglandins, and PPARgamma : Possible relevance to human fibrotic disorders."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.232422999"}], "href": "https://doi.org/10.1073/pnas.232422999"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12397176"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12397176"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Nico Mitro, Leo Vargas, Russell Romeo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "T0901317 is a potent PXR ligand: implications for the biology ascribed to LXR."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2007.03.047"}], "href": "https://doi.org/10.1016/j.febslet.2007.03.047"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17418145"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17418145"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Hyeong-Seok Lim, Han Ju Lee, Keun Seok Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical implications of CYP2D6 genotypes predictive of tamoxifen pharmacokinetics in metastatic breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Oncol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1200/JCO.2007.11.4850"}], "href": "https://doi.org/10.1200/JCO.2007.11.4850"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17761971"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17761971"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "David R Gandara, Tomoya Kawaguchi, John Crowley, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Japanese-US common-arm analysis of paclitaxel plus carboplatin in advanced non-small-cell lung cancer: a model for assessing population-related pharmacogenomics."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Oncol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1200/JCO.2008.20.8793"}], "href": "https://doi.org/10.1200/JCO.2008.20.8793"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19470925"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19470925"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Dione Gardner-Stephen, Jean-Marie Heydel, Amit Goyal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human PXR variants and their differential effects on the regulation of human UDP-glucuronosyltransferase gene expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Drug Metab Dispos (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/dmd.32.3.340"}], "href": "https://doi.org/10.1124/dmd.32.3.340"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14977869"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14977869"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Jatinder Lamba, Vishal Lamba, Stephen Strom, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel single nucleotide polymorphisms in the promoter and intron 1 of human pregnane X receptor/NR1I2 and their association with CYP3A4 expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Drug Metab Dispos (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/dmd.107.016600"}], "href": "https://doi.org/10.1124/dmd.107.016600"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17925385"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17925385"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Khaled Benkali, Aurelie Prémaud, Nicolas Picard, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tacrolimus population pharmacokinetic-pharmacogenetic analysis and Bayesian estimation in renal transplant recipients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Pharmacokinet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2165/11318080-000000000-00000"}], "href": "https://doi.org/10.2165/11318080-000000000-00000"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19902988"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19902988"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Linhao Li, Joseph D Stanton, Antonia H Tolson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bioactive terpenoids and flavonoids from Ginkgo biloba extract induce the expression of hepatic drug-metabolizing enzymes through pregnane X receptor, constitutive androstane receptor, and aryl hydrocarbon receptor-mediated pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pharm Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11095-008-9788-8"}], "href": "https://doi.org/10.1007/s11095-008-9788-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19034627"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19034627"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Hongwei Wang, Madhukumar Venkatesh, Hao Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pregnane X receptor activation induces FGF19-dependent tumor aggressiveness in humans and mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI41514"}], "href": "https://doi.org/10.1172/JCI41514"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21747170"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21747170"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Yasuhiro Miki, Takashi Suzuki, Chika Tazawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Steroid and xenobiotic receptor (SXR), cytochrome P450 3A4 and multidrug resistance gene 1 in human adult and fetal tissues."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Endocrinol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mce.2004.12.005"}], "href": "https://doi.org/10.1016/j.mce.2004.12.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15713537"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15713537"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Kazuma Kiyotani, Taisei Mushiroda, Michiaki Kubo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of genetic polymorphisms in SLCO1B3 and ABCC2 with docetaxel-induced leukopenia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Sci (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1349-7006.2008.00765.x"}], "href": "https://doi.org/10.1111/j.1349-7006.2008.00765.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18294295"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18294295"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Hans Blokzijl, Sara Vander Borght, Lisette I H Bok, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Decreased P-glycoprotein (P-gp/MDR1) expression in inflamed human intestinal epithelium is independent of PXR protein levels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Inflamm Bowel Dis (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ibd.20088"}], "href": "https://doi.org/10.1002/ibd.20088"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17262809"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17262809"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Isabelle Dussault, Hye-Dong Yoo, Min Lin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of an endogenous ligand that activates pregnane X receptor-mediated sterol clearance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0336235100"}], "href": "https://doi.org/10.1073/pnas.0336235100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12569201"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12569201"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Katsuyoshi Kawana, Togo Ikuta, Yasuhito Kobayashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular mechanism of nuclear translocation of an orphan nuclear receptor, SXR."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Pharmacol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/mol.63.3.524"}], "href": "https://doi.org/10.1124/mol.63.3.524"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12606758"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12606758"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Jie Cheng, Xiaochao Ma, Kristopher W Krausz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rifampicin-activated human pregnane X receptor and CYP3A4 induction enhance acetaminophen-induced toxicity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Drug Metab Dispos (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/dmd.109.027565"}], "href": "https://doi.org/10.1124/dmd.109.027565"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19460945"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19460945"}]}, {"type": "r", "ref": 41, "children": [{"type": "t", "text": "Yuping Chen, Grace Kissling, Masahiko Negishi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The nuclear receptors constitutive androstane receptor and pregnane X receptor cross-talk with hepatic nuclear factor 4alpha to synergistically activate the human CYP2C9 promoter."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Pharmacol Exp Ther (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/jpet.105.087072"}], "href": "https://doi.org/10.1124/jpet.105.087072"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15919766"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15919766"}]}, {"type": "r", "ref": 42, "children": [{"type": "t", "text": "Koichiro Mihara, Rithwik Ramachandran, Bernard Renaux, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neutrophil elastase and proteinase-3 trigger G protein-biased signaling through proteinase-activated receptor-1 (PAR1)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.483123"}], "href": "https://doi.org/10.1074/jbc.M113.483123"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24052258"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24052258"}]}, {"type": "r", "ref": 43, "children": [{"type": "t", "text": "Vibeke Andersen, Jane Christensen, Anja Ernst, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polymorphisms in NF-κB, PXR, LXR, PPARγ and risk of inflammatory bowel disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "World J Gastroenterol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3748/wjg.v17.i2.197"}], "href": "https://doi.org/10.3748/wjg.v17.i2.197"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21245992"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21245992"}]}]}]}