Advantages of cell-based high-volume screening assays to assess nuclear receptor activation during drug discovery

Bibliography

• Honkakoski P, Zelko I, Sueyoshi T, Negishi M. The nuclear orphan receptor CAR-retinoid X receptor heterodimer activates the phenobarbital-responsive enhancer module of the CYP2B gene. Mol Cell Biol 1998;18:5652-8
   PubMed Web of Science ®Google Scholar
• Moore LB, Parks DJ, Jones SA, et al. Orphan NRs constitutive androstane receptor and pregnane X receptor share xenobiotic and steroid ligands. J Biol Chem 2000;275:15122-7
   PubMed Web of Science ®Google Scholar
• Kanno Y, Inoue Y, Inouye Y. 5-Aminoimidazole-4-carboxamide-1-b*ribofuranoside (AICAR) prevents nuclear translocation of constitutive androstane receptor by AMP-activated protein kinase (AMPK) independent manner. J Toxicol Sci 2010;35:571-6
   PubMed Web of Science ®Google Scholar
• Saito K, Moore R, Negishi M. p38 mitogen-activated protein kinase regulates NR CAR that activates the CYP2B6 gene. Drug Metab Dispos 2013;41:1170-3
   PubMed Web of Science ®Google Scholar
• Rencurel F, Foretz M, Kaufmann MR, et al. Stimulation of AMP-activated protein kinase is essential for the induction of drug metabolizing enzymes by phenobarbital in human and mouse liver. Mol Pharmacol 2006;70:1925-34
   PubMed Web of Science ®Google Scholar
• Yang H, Garzel B, Heyward S, et al. Metformin represses drug-induced expression of CYP2B6 by modulating the constitutive androstane receptor signaling. Mol Pharmacol 2014;85:249-60
   PubMed Web of Science ®Google Scholar
• Krausova L, Stejskalova L, Wang H, et al. Metformin suppresses pregnane x receptor (PXR)-regulated transactivation of CYP3A4 gene. Biochem Pharmacol 2011;82:1771-80
   PubMed Web of Science ®Google Scholar
• Goodwin B, Moore LB, Stoltz CM, et al. Regulation of the human CYP2B6 gene by the nuclear pregnane X receptor. Mol Pharmacol 2001;60:427-31
   PubMed Web of Science ®Google Scholar
• Orans J, Teotico DG, Redinbo MR. The nuclear xenobiotic receptor pregnane X receptor: recent insights and new challenges. Mol Endocrinol 2005;19:2891-900
   PubMed Web of Science ®Google Scholar
• Umesono K, Evans RM. Determinants of target gene specificity for steroid/thyroid hormone receptors. Cell 1989;57:1139-46
   PubMed Web of Science ®Google Scholar
• Gerbal-Chaloin S, Daujat M, Pascussi JM, et al. Transcriptional regulation of CYP2C9 gene: role of glucocorticoid receptor and constitutive androstane receptor. J Biol Chem 2002;277:209-17
   PubMed Web of Science ®Google Scholar
• Raucy JL, Mueller L, Duan K, et al. Expression and induction of CYP2C P450 enzymes in primary cultures of human hepatocytes. J Pharmacol Exp Ther 2002;302:475-82
   PubMed Web of Science ®Google Scholar
• Synold TW, Dussault I, Forman BM. The orphan NR SXR coordinately regulates drug metabolism and efflux. Nat Med 2001;7:584-90
   PubMed Web of Science ®Google Scholar
• Xie W, Yueh MF, Radominska-Pandya A, et al. Control of steroid, heme, and carcinogen metabolism by nuclear pregnane X receptor and constitutive androstane receptor. Proc Natl Acad Sci USA 2003;100:4150-5
   PubMed Web of Science ®Google Scholar
• Chen C, Staudinger JL, Klaassen CD. NR, pregnane X receptor, is required for induction of UDP-glucuronosyltranferases in mouse liver by pregnenolone-16 alpha-carbonitrile. Drug Metab Dispos 2003;31:908-15
   PubMed Web of Science ®Google Scholar
• Runge-Morris M, Wu W, Kocarek TA. Regulation of rat hepatic hydroxysteroid sulfotransferase (SULT2-40/41) gene expression by glucocorticoids: evidence for a dual mechanism of transcriptional control. Mol Pharmacol 1999;56:1198-206
   PubMed Web of Science ®Google Scholar
• Vyhlidal CA, Rogan PK, Leeder JS. Development and refinement of pregnane X receptor (PXR) DNA binding site model using information theory: insights into PXR-mediated gene regulation. J Biol Chem 2004;279:46779-86
   PubMed Web of Science ®Google Scholar
• Courtois A, Payen L, Guillouzo A, Fardel O. Up-regulation of multidrug resistance-associated protein 2 (MRP2) expression in rat hepatocytes by dexamethasone. FEBS Lett 1999;459:381-5
   PubMed Web of Science ®Google Scholar
• Dussault I, Forman BM. The NR PXR: a master regulator of “homeland” defense. Crit Revin Eukaryotic Gene Expr 2002;12:53-64
   PubMed Web of Science ®Google Scholar
• Fromm MF, Kauffmann HM, Fritz P, et al. The effect of rifampin treatment on intestinal expression of human MRP transporters. Am J Pathol 2000;157:1575-80
   PubMed Web of Science ®Google Scholar
• Geick A, Eichelbaum M, Burk O. NR response elements mediate induction of intestinal MDR1 by rifampiin. J Biol Chem 2001;276:14581-7
   PubMed Web of Science ®Google Scholar
• Maher JM, Cheng X, Slitt AL, et al. Induction of the multidrug resistance-associated protein family of transporters by chemical activators of receptor-mediated pathways in mouse liver. Drug Metab Dispos 2005;33:956-62
   PubMed Web of Science ®Google Scholar
• Stedman CA, Liddle C, Coulter SA, et al. NRs constitutive androstane receptor and pregnane X receptor ameliorate cholestatic liver injury. Proc Natl Acad Sci USA 2005;102:2063-8
   PubMed Web of Science ®Google Scholar
• Sueyoshi T, Kawamoto T, Zelko I, et al. The repressed NR CAR responds to phenobarbital in activating the human CYP2B6 gene. J Biol Chem 1999;274:6043-6
   PubMed Web of Science ®Google Scholar
• Sueyoshi T, Negishi M. Phenobarbital response elements of cytochrome P450 genes and NRs. Annu Rev Pharmacol Toxicol 2001;41:123-43
   PubMed Web of Science ®Google Scholar
• Assem M, Schuetz EG, Leggas M, et al. Interactions between hepatic Mrp4 and Sult2a as revealed by the constitutive androstane receptor and Mrp4 knockout mice. J Biol Chem 2004;279:22250-7
   PubMed Web of Science ®Google Scholar
• Buckley DB, Klaassen CD. Induction of mouse UDP-glucuronosyltransferase mRNA expression in liver and intestine by activators of aryl-hydrocarbon receptor, constitutive androstane receptor, pregnane X receptor, peroxisome proliferator-activated receptor alpha, and nuclear factor erythroid 2-related factor 2. Drug Metab Dispos 2009;37:847-56
   PubMed Web of Science ®Google Scholar
• Ueda A, Hamadeh HK, Webb HK, et al. Diverse roles of the nuclear orphan receptor CAR in regulating hepatic genes in response to phenobarbital. Mol Pharmacol 2002;61:1-6
   PubMed Web of Science ®Google Scholar
• Denison MS, Fisher JM, Whitlock JP Jr. The DNA recognition site for the dioxin-Ah receptor complex. Nucleotide sequence and functional analysis. J Biol Chem 1988;263:17221-4
   PubMed Web of Science ®Google Scholar
• Denison MS, Fisher JM, Whitlock JP Jr. Inducible, receptor-dependent protein-DNA interactions at a dioxin-responsive transcriptional enhancer. Proc Natl Acad Sci USA 1988;85:2528-32
   PubMed Web of Science ®Google Scholar
• Honkakoski P, Negishi M. Regulation of cytochrome P450 (CYP) genes by NRs. Bio Chem J 2000;347:321-37
   PubMed Web of Science ®Google Scholar
• Fahmi O, Ripp S. Evaluation of models for predicting drug-drug interactions due to induction. Exp Opin Drug Metab Toxicol 2010;6:1399-416
   PubMed Web of Science ®Google Scholar
• Bradfield CA, Bjeldanes LF. Structure-activity relationships of dietary indoles: a proposed mechanism of action as modifiers of xenobiotic metabolism. J Toxicol Environ Health 1987;21:311-23
   PubMed Web of Science ®Google Scholar
• Daujat M, Peryt B, Lesca P, et al. Omeprazole, an inducer of human CYP1A1 and 1A2, is not a ligand for the Ah receptor. Biochem Biophys Res Commun 1992;188:820-5
   PubMed Web of Science ®Google Scholar
• Fuhr U, Woodcock BG, Siewert M. Verapamil and drug metabolism by the cytochrome P450 isoform CYP1A2. Eur J Clin Pharmacol 1992;42:463-4
   PubMed Web of Science ®Google Scholar
• Gu L, Gonzalez FJ, Kalow W, Tang BK. Biotransformation of caffeine, paraxanthine, theobromine and theophylline by cDNA-expressed human CYP1A2 and CYP2E1. Pharmacogenetics 1992;2:73-7
   PubMedGoogle Scholar
• Lemoine A, Gautier JC, Azoulay D, et al. Major pathway of imipramine metabolism is catalyzed by cytochromes P450 1A2 and P4503A4 in human liver. Mol Pharmacol 1993;43:827-32
   PubMed Web of Science ®Google Scholar
• Madsen H, Rasmussen BB, Brosen K. Imipramine demethylation in vivo: impact of CYP1A2, CYP2C19, and CYP3A4. Clin Pharmacol Ther 1997;61:319-24
   PubMed Web of Science ®Google Scholar
• Pastrakuljic A, Tang BK, Roberts EA, Kalow W. Distinction of CYP1A1 and CYP1A2 activity by selective inhibition using fluvoxamine and isosafrole. Biochem Pharmacol 1997;53:531-8
   PubMed Web of Science ®Google Scholar
• Ciolino HP, Daschner PJ, Wang TT, Yeh GC. Effect of curcumin on the aryl hydrocarbon receptor and cytochrome P450 1A1 in MCF-7 human breast carcinoma cells. Biochem Pharmacol 1998;56:197-206
   PubMed Web of Science ®Google Scholar
• Ciolino HP, Daschner PJ, Yeh GC. Dietary flavonols quercetin and kaempferol are ligands of the aryl hydrocarbon receptor that affect CYP1A1 transcription differentially. Biochem J 1999;340(Pt 3):715-22
   PubMed Web of Science ®Google Scholar
• Heath-Pagliuso S, Rogers WJ, Tullis K, et al. Activation of the Ah receptor by tryptophan and tryptophan metabolites. Biochemistry 1998;37:11508-15
   PubMed Web of Science ®Google Scholar
• Barbier O, Duran-Sandocal D, Pineda-Torra I, et al. Peroxisome proliferator-activated receptor alpha induces hepatic expression of the human bile acid glucuronidating UDP-glucuronosyltransferase 2B4 enzyme. J Biol Chem 2003;278:32852-60
   PubMed Web of Science ®Google Scholar
• Barbier O, Fontaine C, Fruchart JC, Staels B. Genomic and non-genomic interactions of PPARalpha with xenobiotic-metabolizing enzymes. Trends Endocrinol Metab 2004;15:324-30
   PubMed Web of Science ®Google Scholar
• Klein K, Thomas M, Winter S, et al. PPARA: a novel genetic determinant of CYP3A4 in vitro and in vivo. Clin Pharmacol Ther 2012;91:1044-52
   PubMed Web of Science ®Google Scholar
• Thomas M, Burk O, Klumpp B, et al. Direct transcriptional regulation of human hepatic cytochrome P450 3A4 (CYP3A4) by peroxisome proliferator-activated receptor alpha (PPARalpha). Mol Pharmacol 2013;83:709-18
   PubMed Web of Science ®Google Scholar
• Johnson EF, Palmer CN, Griffin KJ, Hsu MH. Role of the peroxisome proliferator-activated receptor in cytochrome P450 4A gene regulation. FASEB J 1996;10:1241-8
   PubMed Web of Science ®Google Scholar
• Aleksunes LM, Klaassen CD. Coordinated regulation of hepatic phase I and II drug-metabolizing genes and transporters using AhR-, CAR-, PXR-, PPARalpha-, and Nrf2-null mice. Drug Metab Dispos 2012;40:1366-79
   PubMed Web of Science ®Google Scholar
• Handschin C, Meyer UA. Regulatory network of lipid-sensing NRs: roles for CAR, PXR, LXR, and FXR. Arch Biochem Biophys 2005;433:387-96
   PubMed Web of Science ®Google Scholar
• Klaassen CD, Slitt AL. Regulation of hepatic transporters by xenobiotic receptors. Curr Drug Metab 2005;6:309-28
   PubMed Web of Science ®Google Scholar
• Xu C, Li CY, Kong AN. Induction of phase I, II and III drug metabolism/transport by xenobiotics. Arch Pharm Res 2005;28:249-68
   PubMed Web of Science ®Google Scholar
• Pascussi JM, Drocourt L, Fabre JM, et al. Dexamethasone induces pregnane x receptor and retinoid x receptor-alpha expression in human hepatocytes: synergistic increase of CYP3A4 induction by pregnane x receptor activators. Mol Pharmacol 2000;58:361-72
   PubMed Web of Science ®Google Scholar
• Li L, Sinz MW, Zimmermann K, Wang H. An insulin-like growth factor 1 receptor inhibitor induces CYP3A4 expression through a pregnane x receptor-independent, noncanonical constitutive androstane receptor-related mechanism. J Pharmacol Exp Ther 2012;340:688-97
   PubMed Web of Science ®Google Scholar
• Li H, Chen T, Cottrell J, Wang H. Nuclear translocation of adenoviral-enhanced yellow fluorescent protein-tagged-human constitutive androstane receptor (hCAR): a novel tool for screening hCAR activators in human primary hepatocytes. Drug Metab Dispos 2009;37:1098-106
   PubMed Web of Science ®Google Scholar
• Hart SN, Li Y, Nakamoto K, et al. A comparison of whole genome gene expression profiles of hepaRG cells and HepG2 cells to primary human hepatocytes and human liver tissues. Drug Metab Dispos 2010;38:988-94
   PubMed Web of Science ®Google Scholar
• Darnell M, Ulvestad M, Ellis E, et al. In vitro evaluation of major in vivo drug metabolic pathways using primary human hepatocytes and HepaRG cells in suspension and a dynamic three-dimensional bioreactor system. J Pharmacol Exp Ther 2012;343:134-44
   PubMed Web of Science ®Google Scholar
• Godoy P, Hewitt NJ, Albrecht J, et al. Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanism of hepatotoxicity, cell signaling and ADME. Arch Toxicol 2013;87:1315-530
   PubMed Web of Science ®Google Scholar
• Lee SA, da Y N, Kang E, et al. Spheroid-based three-dimensional liver-on-a-chip to investigate heaptocyte-hepatic stellate cell interactions and flow effects. Lab Chip 2013;13:3529-37
   PubMed Web of Science ®Google Scholar
• Kublbeck J, Laitinen T, Jyrkkarinne J, et al. Use of comprehensive screening methods to detect selective human CAR activators. Biochem Pharmacol 2011;82:1994-2007
   PubMed Web of Science ®Google Scholar
• Raucy J, Lasker J. Current in vitro high throughput screening approaches to assess NR activation. Curr Drug Metab 2010;11:806-14
   PubMed Web of Science ®Google Scholar
• Shukla SJ, Nguyen D-T, MacArhur R, et al. Identification of Pregnane X Receptor Ligands using time-resolved fluorescence resonance energy transfer and quantitative high-throughput screening. Assay Drug Dev Tech 2009;7:143-69
   PubMed Web of Science ®Google Scholar
• Raucy JL, Lasker JM. Cell-based systems to assess NR activation and their use in drug development. Drug Metab Rev 2013;45:101-9
   PubMed Web of Science ®Google Scholar
• Chu V, Einolf HJ, Evers R, et al. In vitro and in vivo induction of cytochrome P450: a survey of the current practices and recommendations: a pharmaceutical research and manufacturers of America perspective. Drug Met Disp 2009;37:1339-54
   PubMed Web of Science ®Google Scholar
• Fahmi OA, Raucy JL, Ponce E, et al. Utility of DPX2 cells for predicting CYP3A induction-mediated drug-drug interactions and associated structure-activity relationships. Drug Metab Dispos 2012;40:2204-11
   PubMed Web of Science ®Google Scholar
• Hewitt N, Gomez-Lechen J, Houston J, et al. Primary hepatocytes: current understanding of the regulation of metabolic enzymes and transporter proteins, and pharmaceutical practice for the use of hepatocyte in metabolism, enzyme induction, transporter, clearance and heaptotoxicity studies. Drug Metab Rev 2007;39:159-234
   PubMed Web of Science ®Google Scholar
• Luo G, Cunningham M, Kim S, et al. CYP3A4 induction by drugs: correlation between a pregnane X receptor reporter gene assay and CYP3A4 expression in human hepatocytes. Drug Metab Dispos 2002;30:795-804
   PubMed Web of Science ®Google Scholar
• Sinz M, Kim S, Zhu Z, et al. Evaluation of 170 xenobiotics as transactivators of human pregnane X receptor (hPXR) and correlation to known to CYP3A4 drug interactions. Curr Drug Metab 2006;7:375-88
   PubMed Web of Science ®Google Scholar
• Zhu Z, Kim S, Chen T, et al. Correlation of high-throughput pregnane x receptor transactivation and binding assays. J Biomol Screen 2004;9:533-40
   PubMed Web of Science ®Google Scholar
• Zhu Z, Puglishi J, Connors D, et al. Use of cryopreserved transiently transfected cells in high-throughput pregnane X receptor transactivation assay. J Biomol Screen 2007;12:248-54
   PubMed Web of Science ®Google Scholar
• Fery Y, Mueller SO, Schrenk D. Development of stably transfected human and rat hepatoma cell lines for the species-specific assessment of xenobiotic response enhancer module (XREM)-dependent induction of drug metabolism. Toxicology 2010;277:11-19
   PubMed Web of Science ®Google Scholar
• Kublbeck J, Reinisalo M, Mustonen R, Honkakoski P. Up-regulation of CYP expression in hepatoma cells stably transfected by chimeric NRs. Eur J Pharm Sci 2010;40:263-72
   PubMed Web of Science ®Google Scholar
• Lemaire G, De Sousa G, Rahmani R. A PXR reporter gene assay in a stable cell culture system: CYP3A4 and CYP2B6 induction by pesticides. Biochem Pharmacol 2004;68:2347-58
   PubMed Web of Science ®Google Scholar
• Raucy JL, Warfe L, Yueh MF, Allen SW. A cell-based reporter gene assay for determining induction of CYP3A4 in a high volume system. J Pharmacol Exp Ther 2002;303:412-23
   PubMed Web of Science ®Google Scholar
• Sekimoto M, Sano S, Hosaka T, et al. Establishment of a stable human cell line, HPL-A3, for use in reporter gene assays of cytochrome P350 3A inducers. Biol Pharm Bull 2012;35:677-85
   PubMed Web of Science ®Google Scholar
• Yueh MF, Kawahara M, Raucy JL. High volume bioassays to assess CYP3A4-mediated drug interactions: induction and inhibition in a single cell line. Drug Metabol Dispos 2005;33:38-48
   PubMed Web of Science ®Google Scholar
• Bisson WH, Koch DC, O’Donnell EF, et al. Modeling of the Aryl hydrocarbon receptor (AhR) ligand binding domain and its utility in virtual ligand screening to predict new AhR ligands. J Med Chem 2009;52:5635-41
   PubMed Web of Science ®Google Scholar
• He G, Zhao J, Brennan JC, et al. Cell-based assays for identification of aryl hydrocarbon receptor (AhR) activators. In: Caldwell Gary W, Yan Z, editors. Optimization in drug discovery: in vitro methods. 2nd edition. Humana Press, New York; 2014. p. 221-36
   Google Scholar
• Yueh MF, Kawahara M, Raucy J. Cell-based high-throughput bioassays to assess induction and inhibition of CYP1A enzymes. Toxicol In Vitro 2005;19:275-87
   PubMed Web of Science ®Google Scholar
• Allen SW, Mueller L, Williams SN, et al. The use of a high-volume screening procedure to assess the effects of dietary flavonoids on human CYP1A1 expression. Drug Metab Dispos 2001;29:1074-9
   PubMed Web of Science ®Google Scholar
• Cui X, Palamanda J, Norton L, et al. A high-throughput cell-based reporter gene system for measurement of CYP1A1 induction. J Pharmacol Toxicol Methods 2002;47:143-51
   PubMed Web of Science ®Google Scholar
• Bovee TE, Hoogenboom LA, Hammers AR, et al. Validation and use of the CALUX-bioassay for the determination of dioxins and PCBs in bovine milk. Food Addit Contam 1998;15:863-75
   PubMedGoogle Scholar
• Garrison PM, Tullis K, Aarts JM, et al. Species-specific recombinant cell lines as bioassay systems for the detection of 2,3,7,8-tetrachlorodibenzo-p-dioxin-like chemicals. Fundam Appl Toxicol 1996;30:194-203
   PubMedGoogle Scholar
• Murk AJ, Legler J, Denison MS, et al. Chemical-activated luciferase gene expression (CALUX): a novel in vitro bioassay for Ah receptor active compounds in sediments and pore water. Fundam Appl Toxicol 1996;33:149-60
   PubMedGoogle Scholar
• Seidel SD, Li V, Winter GM, et al. Ah receptor-based chemical screening bioassays: application and limitations for the detection of Ah receptor agonists. Toxicol Sci 2000;55:107-15
   PubMed Web of Science ®Google Scholar
• Takeuchi S, Iida M, Tabushita H, et al. In vitro screening for aryl hydrocarbon receptor agonisitic activity in 200 pesticides using a highly sensitive reporter cell line, DR-EcoScreen cells, and in vivo mouse liver cytochrome P450-1A induction by propanil, diuron and linuron. Chemosphere 2008;74:155-65
   PubMed Web of Science ®Google Scholar
• di Masi A, De Marinis E, Ascenzi P, Marino M. NRs CAR and PXR: molecular, functional, and biomedical aspects. Mol Aspects Med 2009;30:297-343
   PubMed Web of Science ®Google Scholar
• Xie W, Barwick JL, Simon CM, et al. Reciprocal activation of xenobiotic response genes by NRs SXR/PXR and CAR. Genes Dev 2000;14:3014-23
   PubMed Web of Science ®Google Scholar
• Fahmi OA, Boldt S, Kish M, et al. Prediction of drug-drug interactions from in vitro induction data: application of the relative induction score approach using cryopreserved human hepatocytes. Drug Metab Dispos 2008;36:1971-4
   PubMed Web of Science ®Google Scholar
• Sinz M, Wallace G, Sahi J. Current industrial practices in assessing CYP450 enzyme induction: preclinical and clinical. AAPS J 2008;10:391-400
   PubMed Web of Science ®Google Scholar
• Schuster D, Langer T. The identification of ligand features essential for PXR activation by pharmacophore modeling. J Chem Inf Model 2005;45:431-9
   PubMed Web of Science ®Google Scholar
• Waxman DJ, Azaroff L. Phenobarbital induction of cytochrome P-450 gene expression. Biochem J 1992;281(Pt 3):577-92
   PubMed Web of Science ®Google Scholar
• Burke TJ, Loniello KR, Beebe JA, Ervin KM. Development and application of fluorescence polarization assays in drug discovery. Comb Chem High Throughput Screen 2003;6:183-94
   PubMed Web of Science ®Google Scholar
• Lee SS, Buters JT, Pineau T, et al. Role of CYP2E1 in the hepatotoxicity of acetaminophen. J Biol Chem 1996;271:12063-7
   PubMed Web of Science ®Google Scholar
• Thummel KE, Lee CA, Kunze KL, et al. Oxidation of acetaminophen to N-acetyl-p-aminobenzoquinone imine by human CYP3A4. Biochem Pharmacol 1993;45:1563-9
   PubMed Web of Science ®Google Scholar
• Tonge RP, Kelly EJ, Bruschi SA, et al. Role of CYP1A2 in the hepatotoxicity of acetaminophen: investigations using Cyp1a2 null mice. Toxicol Appl Pharmacol 1998;153:102-8
   PubMed Web of Science ®Google Scholar
• Raucy JL, Lasker JM, Lieber CS, Black M. Acetaminophen activation by human liver cytochromes P450IIE1 and P450IA2. Arch Biochem Biophys 1989;271:270-83
   PubMed Web of Science ®Google Scholar
• Cheng J, Xiaochao M, Krausz K, et al. Rifampicin-activated human pregnane X receptor and CYP3A4 induction enhance acetaminophen-induced toxicity. Drug Metab Dispos 2009;37:1611-21
   PubMed Web of Science ®Google Scholar
• Woods CG, Heuvel JP, Rusyn I. Genomic profiling in NR-mediated toxicity. Toxicol Pathol 2007;35:474-94
   PubMed Web of Science ®Google Scholar
• Zhang J, Wei Y, Hu B, et al. Activation of human stearoyl-coenzyme A desaturase 1 contributes to the lipogenic effect of PXR in HepG2 cells. PLoS One 2013;8:e67959
   PubMedGoogle Scholar
• Chai X, Zeng S, Xie W. NRs PXR and CAR: implications for drug metabolism regulation, pharmacogenomics and beyond. Expert Opin Drug Metab Toxicol 2013;9:253-66
   PubMed Web of Science ®Google Scholar
• Zhou C, Tabb MM, Nelson EL, et al. Mutual repression between steroid and xenobiotic receptor and NF-kappaB signaling pathways links xenobiotic metabolism and inflammation. J Clin Invest 2006;116:2280-9
   PubMed Web of Science ®Google Scholar
• Zhai Y, Pai HV, Zhou J, et al. Activation of pregnane x receptor disrupts glucocorticoid and mineralocorticoid homeostasis. Mol Endocrinol 2007;21:138-47
   PubMed Web of Science ®Google Scholar
• Bauer B, Hartz AM, Fricker G, Miller DS. Pregnane X receptor up-regulation of P-glycoprotein expression and transport function at the blood-brain barrier. Mol Pharmacol 2004;66:413-19
   PubMed Web of Science ®Google Scholar
• Bauer B, Hartz AM, Lucking JR, et al. Coordinated NR regulation of the efflux transporter, Mrp2, and the phase-II metabolizing enzyme, GSTpi, at the blood-brain barrier. J Cereb Blood Flow Metab 2008;28:1222-34
   PubMed Web of Science ®Google Scholar
• Bauer B, Yang X, Hartz AM, et al. In vivo activation of human pregnane X receptor tightens the blood-brain barrier to methadone through P-glycoprotein up-regulation. Mol Pharmacol 2006;70:1212-19
   PubMed Web of Science ®Google Scholar
• Lombardo L, Pellitteri R, Balazy M, Cardile V. Induction of NRs and drug resistance in the brain microvascular endothelial cells treated with antiepileptic drugs. Curr Neurovasc Res 2008;5:82-92
   PubMed Web of Science ®Google Scholar
• Yu XQ, Xue CC, Wang G, Zhou SF. Multidrug resistance associated proteins as determining factors of pharmacokinetics and pharmacodynamics of drugs. Curr Drug Metab 2007;8:787-802
   PubMed Web of Science ®Google Scholar
• Zheng XE, ZWang Z, Liao MZ, et al. Human PXR-mediated induction of intestinal CYP3A4 attenuates 1a,25-dihydroxyvitamin D3 function in human colon adenocarcinoma LS180 cells. Biochem Pharmacol 2012;84:391-401
   PubMed Web of Science ®Google Scholar
• Pascussi JM, Robert A, Nguyen M, et al. Possible involvement of pregnane X receptor-enhanced CYP24 expression in drug-induced osteomalacia. J Clin Invest 2005;115:177-86
   PubMed Web of Science ®Google Scholar
• Zhou C, Assem M, Tay JC, et al. Steroid and xenobiotic receptor and vitamin D receptor crosstalk mediates CYP24 expression and drug-induced osteomalacia. J Clin Invest 2006;116:1703-12
   PubMed Web of Science ®Google Scholar
• Konno Y, Kodama S, Moore R, et al. Nuclear xenobiotic receptor pregnane x receptor locks corepressor silencing mediator for retinoid and thyroid hormone receptors (SMRT) onto the CYP24A1 promoter to attenuate vitamin D3 activation. Mol Pharmacol 2009;75:265-71
   PubMed Web of Science ®Google Scholar
• Brodie MJ, Boobis AR, Hillyard CJ, et al. Effect of rifampicin and isoniazid on vitamin D metabolism. Clin Pharmacol Ther 1982;32:525-30
   PubMed Web of Science ®Google Scholar
• Pack AM, Morrell MJ. Epilepsy and bone health in adults. Epilepsy Behav 2004;5:S24-9
   PubMed Web of Science ®Google Scholar
• Blumberg B, Sabbagh W Jr, Juguilon H, et al. SXR, a novel steroid and xenobiotic-sensing NR. Genes Dev 1998;12:3195-205
   PubMed Web of Science ®Google Scholar
• Kliewer SA, Moore JT, Wade L, et al. An orphan NR activated by pregnanes defines a novel steroid signaling pathway. Cell 1998;92:73-82
   PubMed Web of Science ®Google Scholar
• Forman BM, Tzameli I, Choi HS, et al. Androstane metabolites bind to and deactivate the NR CAR-beta·. Nature 1998;395:612-15
   PubMed Web of Science ®Google Scholar
• Biswas A, Mani S, Redinbo MR, et al. Elucidating the ’Jekyll and Hyde’ nature of PXR: the case for discovering antagonists or allosteric antagonists. Pharm Res 2009;26:1807-15
   PubMed Web of Science ®Google Scholar
• Kittayaruksakul S, Zhao W, Xu M, et al. Identification of three novel natural product compounds that activate PXR and CAR and inhibit inflammation. Pharm Res 2013;30:2199-208
   PubMed Web of Science ®Google Scholar
• Gao J, Xie W. Targeting xenobiotic receptors PXR and CAR for metabolic diseases. Trends Pharmacol Sci 2012;33:552-8
   PubMed Web of Science ®Google Scholar
• Zhou J, Liu M, Zhai Y, Xie W. The anti-apoptotic role of pregnane x receptor in human colon cancer cells. Mol Endocrinol 2008;22:868-80
   PubMed Web of Science ®Google Scholar
• Verma S, Tabb MM, Blumberg B. Activation of the steroid and xenobiotic receptor, SXR, induces apoptosis in breast cancer cells. BMC Cancer 2009;9:3
   PubMed Web of Science ®Google Scholar
• Zhang B, Cheng Q, Ou Z, et al. Pregnane X receptor as a therapeutic target to inhibit androgen activity. Endocrinology 2010;151:5721-9
   PubMed Web of Science ®Google Scholar
• DiNatale BC, Murray IA, Schroeder JC, et al. Kynurenic acid is a potent endogenous aryl hydrocarbon receptor ligand that synergistically induces interleukin-6 in the presence of inflammatory signaling. Toxicol Sci 2010;115:89-97
   PubMed Web of Science ®Google Scholar
• Opitz CA, Litzenburger UM, Sahm F, et al. An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor. Nature 2011;478:197-203
   PubMed Web of Science ®Google Scholar
• Eloranta JJ, Kullak-Ublick GA. Coordinate transcriptional regulation of bile acid homeostasis and drug metabolism. Arch Biochem Biophys 2005;433:397-412
   PubMed Web of Science ®Google Scholar
• Moreau A, Vilarem MJ, Maurel P, Pascussi JM. Xenoreceptors CAR and PXR activation and consequences on lipid metabolism, glucose homeostasis, and inflammatory response. Mol Pharm 2008;5:35-41
   PubMed Web of Science ®Google Scholar
• Zhou C, Verma S, Blumberg B. The steroid and xenobiotic receptor (SXR), beyond xenobiotic metabolism. NR Signaling 2009;7:1-21
   Google Scholar
• Zhang J, Huang W, Qatanani M, et al. The constitutive androstane receptor and pregnane X receptor function coordinately to prevent bile acid-induced hepatotoxicity. J Biol Chem 2004;279:49517-22
   PubMed Web of Science ®Google Scholar
• Khogali AM, Chazan BI, Metcalf VJ, Ramsay JH. Hyperlipidaemia as a complication of rifampicin treatment. Tubercle 1974;55:231-3
   PubMedGoogle Scholar
• Lu TT, Makishima M, Repa JJ, et al. Molecular basis for feedback regulation of bile acid synthesis by NRs. Mol Cell 2000;6:507-15
   PubMed Web of Science ®Google Scholar
• Rysa J, Buler M, Savolainen MJ, et al. Pregnane X receptor agonists impair postprandial glucose tolerance. Clin Pharmacol Ther 2013;93:556-63
   PubMed Web of Science ®Google Scholar
• Hu G, Xu C, Staudinger JL. Pregnane X receptor is SUMOylated to repress the inflammatory response. J Pharmacol Exp Ther 2010;335:342-50
   PubMed Web of Science ®Google Scholar
• Chen T. NR drug discovery. Curr Opin Chem Biol 2008;12:1-9
   PubMed Web of Science ®Google Scholar
• Ekins S, Erickson JA. A pharmacophore for human pregnane X receptor ligands. Drug Metab Dispos 2002;30:96-9
   PubMed Web of Science ®Google Scholar
• Moore LB, Maglich JM, McKee DD, et al. Pregnane X receptor (PXR), constitutive androstane receptor (CAR), and benzoate X receptor (BXR) define three pharmacologically distinct classes of NRs. Mol Endocrinol 2002;16:977-86
   PubMed Web of Science ®Google Scholar
• Auerbach SS, Ramsden R, Stoner MA, et al. Alternatively spliced isoforms of the human constitutive androstane receptor. Nucl Acids Res 2003;31:3194-207
   PubMed Web of Science ®Google Scholar
• Savkur RS, Wu Y, Bramlett KS, et al. Alternative splicing within the ligand binding domain of the human constitutive androstane receptor. Mol Genet Metab 2003;80:216-26
   PubMed Web of Science ®Google Scholar
• Lamba JK, Lamba V, Yasuda K, et al. Expression of constitutive androstane receptor splice variants in human tissues and their functional consequences. J Pharmacol Exp Ther 2004;311:811-21
   PubMed Web of Science ®Google Scholar
• Baes M, Gulick T, Choi HS, et al. A new orphan member of the nuclear hormone receptor superfamily that interacts with a subset of retinoic acid response elements. Mol Cell Biol 1994;14:1544-52
   PubMed Web of Science ®Google Scholar
• Zelko I, Sueyoshi T, Kawamoto T, et al. The peptide near the C terminus regulates receptor CAR nuclear translocation induced by xenochemicals in mouse liver. Mol Cell Biol 2001;21:2838-46
   PubMed Web of Science ®Google Scholar
• Auerbach SS, Stoner MA, Su S, Omiecinski CJ. Retinoid X receptor-alpha-dependent transactivation by a naturally occurring structural variant of human constitutive androstane receptor (NR1I3). Mol Pharmacol 2005;68:1239-53
   PubMed Web of Science ®Google Scholar
• Faucette S, Zhang TC, Moore R, et al. Relative activation of human pregnane X receptor versus constitutive androstane receptor defines distinct classes of CYP2B6 and CYP3A4 inducers. J Pharmacol Exp Ther 2007;320:72-80
   PubMed Web of Science ®Google Scholar
• Chen T, Tompkins LM, Li L, et al. A single amino acid controls the functional switch of human constitutive androstane receptor (CAR) 1 to the xenobiotic-sensitive splicing variant CAR3. J Pharmacol Ther 2010;332:106-15
   PubMed Web of Science ®Google Scholar
• Maglich JM, Parks DJ, Moore LB, et al. Identification of a novel human CAR agonist and its use in the identification of CAR target genes. J Biol Chem 2003;278:17277-83
   PubMed Web of Science ®Google Scholar
• Tzameli I, Pissios P, Schuetz EG, Moore DD. The xenobiotic compound 1,4-Bis[2-(3,5-Dicholorpyridyloxy)] benzene is an agonist ligand for the NR CAR. Mol Cell Biol 2000;20:2951-8
   PubMed Web of Science ®Google Scholar
• Omiecinski CJ, Coslo DM, Chen T, et al. Multi-species analyses of direct activators of the constitutive androstane receptor. Toxicol Sci 2011;123:550-62
   PubMed Web of Science ®Google Scholar
• Jones SA, Moore LB, Shenk JL, et al. The pregnane X receptor: a promiscuous xenobiotic receptor that has diverged during evolution. Mol Endocrinol 2000;14:27-39
   PubMed Web of Science ®Google Scholar
• Bertilsson G, Heidrich J, Svensson K, et al. Identification of a human NR defines a new signaling pathway for CYP3A induction. Proc Natl Acad Sci USA 1998;95:12208-13
   PubMed Web of Science ®Google Scholar
• Chen J, Tran C, Xiao L, et al. Co-induction of CYP3A12 and 3A26 in dog liver slices by xenobiotics: species difference between human and dog CYP3A induction. Drug Metab Lett 2009;3:61-6
   PubMedGoogle Scholar
• Bussiere JL. Species selection considerations for preclinical toxicology studies for biotherapeutics. Expert Opin Drug Metab Toxicol 2008;4:871-7
   PubMed Web of Science ®Google Scholar