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Pregnane X receptor

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 606

Nomenclature: Pregnane X receptor

Systematic Nomenclature: NR1I2

Family: 1I. Vitamin D receptor-like receptors

Contents:

Gene and Protein Information Click here for help
Species AA Chromosomal Location Gene Symbol Gene Name Reference
Human 434 3q13.33 NR1I2 nuclear receptor subfamily 1 group I member 2 2,4,18
Mouse 431 16 B3 Nr1i2 nuclear receptor subfamily 1, group I, member 2 18
Rat 431 11q21 Nr1i2 nuclear receptor subfamily 1, group I, member 2 39
Previous and Unofficial Names Click here for help
BXR | Orphan nuclear receptor PAR1 | PXR | steroid and xenobiotic receptor | SXR | orphan nuclear receptor PXR | ONR1 | PAR2 | pregnane-activated receptor | nuclear receptor subfamily 1, group I, member 2 | nuclear receptor subfamily 1
Database Links Click here for help
Alphafold O75469 (Hs), O54915 (Mm), Q9R1A7 (Rn)
CATH/Gene3D 3.30.50.10
ChEMBL Target CHEMBL3401 (Hs), CHEMBL1743244 (Mm), CHEMBL2146315 (Rn)
DrugBank Target O75469 (Hs)
Ensembl Gene ENSG00000144852 (Hs), ENSMUSG00000022809 (Mm), ENSRNOG00000002906 (Rn)
Entrez Gene 8856 (Hs), 18171 (Mm), 84385 (Rn)
Human Protein Atlas ENSG00000144852 (Hs)
KEGG Gene hsa:8856 (Hs), mmu:18171 (Mm), rno:84385 (Rn)
OMIM 603065 (Hs)
Pharos O75469 (Hs)
RefSeq Nucleotide NM_003889 (Hs), NM_022002 (Hs), NM_033013 (Hs), NM_010936 (Mm), NM_001098404 (Mm), NM_052980 (Rn)
RefSeq Protein NP_148934 (Hs), NP_003880 (Hs), NP_071285 (Hs), NP_001091874 (Mm), NP_035066 (Mm), NP_443212 (Rn)
SynPHARM 6467 (in complex with hyperforin)
6465 (in complex with SR12813)
UniProtKB O75469 (Hs), O54915 (Mm), Q9R1A7 (Rn)
Wikipedia NR1I2 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Tethered PXR-LBD/SRC-1p - apoprotein
PDB Id:  3CTB
Resolution:  2.0Å
Species:  Human
References:  33
Image of receptor 3D structure from RCSB PDB
Description:  Tethered PXR-LBD/SRC-1p complexed with SR-12813
PDB Id:  3HVL
Ligand:  SR12813
Resolution:  2.1Å
Species:  Human
References:  33
Natural/Endogenous Ligands Click here for help
17β-estradiol
3-keto-lithocholic acid
lithocholic acid
Comments: Xenobiotics, steroids and benzoates have been proposed as the natural ligands

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists Click here for help
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
garcinoic acid Small molecule or natural product Hs Agonist 6.5 pKd 1
⤷ pKd 6.5 (Kd 3.3x10-7 M) [1]
Description: Binding affinity to hPXR ligand binding domain determined using an isothermic titration calorimetry (ITC) assay.
hyperforin Small molecule or natural product Click here for species-specific activity table Hs Agonist 7.6 pEC50 22,34
⤷ pEC50 7.6 [22,34]
SR12813 Small molecule or natural product Ligand has a PDB structure Hs Agonist 6.7 pEC50 16
⤷ pEC50 6.7 [16]
pregnenolone-16α-carbonitrile Small molecule or natural product Mm Agonist 6.5 pEC50 18
⤷ pEC50 6.5 [18]
(+)-S20 Small molecule or natural product Hs Agonist 6.4 pEC50 23
⤷ pEC50 6.4 [23]
dexamethasone Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Mm Agonist 6.1 pEC50 18
⤷ pEC50 6.1 [18]
schisandrin A Small molecule or natural product Mm Agonist 5.9 pEC50 24
⤷ pEC50 5.9 [24]
garcinoic acid Small molecule or natural product Hs Agonist 5.9 pEC50 1
⤷ pEC50 5.9 (EC50 1.3x10-6 M) [1]
Description: Agonist activity determined using a proprietary AlphaScreen method.
rifampicin Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 5.5 – 6.0 pEC50 4,20
⤷ pEC50 5.5 – 6.0 [4,20]
schisandrin A Small molecule or natural product Hs Agonist 5.7 pEC50 24
⤷ pEC50 5.7 [24]
S20 Small molecule or natural product Hs Agonist 5.7 pEC50 23
⤷ pEC50 5.7 [23]
lovastatin Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Full agonist 5.3 – 6.0 pEC50 20
⤷ pEC50 5.3 – 6.0 (EC50 5x10-6 – 1x10-6 M) [20]
5β-cholestane-3α,7α,12α-triol Small molecule or natural product Mm Agonist 5.5 pEC50 8
⤷ pEC50 5.5 [8]
paclitaxel Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 5.3 pEC50 30
⤷ pEC50 5.3 [30]
5β-cholestane-3α,7α,12α-triol Small molecule or natural product Hs Agonist 5.3 pEC50 13
⤷ pEC50 5.3 [13]
lithocholic acid Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Agonist 5.1 pEC50 28
⤷ pEC50 5.1 [28]
mifepristone Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Agonist ~5.0 pEC50 20
⤷ pEC50 ~5.0 (EC50 ~1x10-5 M) [20]
3-keto-lithocholic acid Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Agonist 4.8 pEC50 28
⤷ pEC50 4.8 [28]
5β-pregnane-3,20-dione Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 6.4 pIC50 16
⤷ pIC50 6.4 (IC50 4x10-7 M) [16]
17β-estradiol Small molecule or natural product Approved drug Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Agonist - - 16
⤷ [16]
clotrimazole Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Agonist - - 2
⤷ [2]
nifedipine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Agonist - - 2
⤷ [2]
vitamin K2 Small molecule or natural product Mm Agonist - - 31
⤷ [31]
phenobarbital Small molecule or natural product Approved drug Ligand has a PDB structure Hs Agonist - - 20
⤷ [20]
View species-specific agonist tables
Agonist Comments
Some environmental xenobiotics (e.g. polychlorinated biphenyls or PCBs, 1,1-dichloro-2,2-bis (p-chlorophenyl)ethylene)) [26,35], and pesticides (e.g. transnonachlor and chlordane) [26] have also been shown to activate PXR.
Antagonists Click here for help
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
trabectedin Small molecule or natural product Approved drug Ligand has a PDB structure Mm Antagonist 8.5 pIC50 30
⤷ pIC50 8.5 [30]
Antagonist Comments
The notion that Ecteinascidin 743 (ET-743) as a PXR antagonist is controversial. It was thought the inhibitory effect may result from the cytotoxicity of this potent antineoplastic agent.
Immunopharmacology Comments
PXR is validated target for immune and inflammatory diseases. Antibacterial-independent PXR-mediated efficacy of rifaximin in the treament of irritable bowel syndrome (IBS; FDA approved in 2015), has confirmed PXR as an IBS molecular target. Selective PXR ligands are being actively pursued, as tools to fully investigate the therapeutic relevance of the receptor.
DNA Binding Click here for help
Structure:  Heterodimer, RXR partner
HRE core sequence:  AGGTCA
Response element:  DR3, Other - see comments
DNA Binding Comments
The PXR forms a heterodimer with RXR, a requirement for binding and activation. The heterodimers formed between PXR and RXR can interact with DR-3 (TGAACTn3TGAACT) (3); ER6 (TGAACTn6AGGTCA) ER6 (5) (This ER6 was also termed IR6 in ref #2); DR4 (6, 33); ER8 (7); IR0 (8) or PBRE (9, 31).
Co-binding Partners Click here for help
Name Interaction Effect Reference
PIT1 Physical Cellular localization 12
Main Co-regulators Click here for help
Name Activity Specific Ligand dependent AF-2 dependent Comments References
NCOA1 Co-activator No No No 18
NRIP1 Co-activator No No No 5
PPARGC1A Co-activator No No No 3
FOXO1 Co-activator No No No 19
NR0B2 Co-repressor No No No 25
GRIP1 Co-activator No No No 29
NCOR2 Co-repressor No No No 30,32
Main Target Genes Click here for help
Name Species Effect Technique Comments References
cytochrome P450 Human Activated Transient transfection, EMSA, Other mCYP3A11, rCYP3A23, hCYP3A4, hCYP2C8, hCYP2C9, mCYP2B10, hCYP2B6 (h-human,m-mouse,r-rat) 2,4,6,9,14,18,30,36
Slco1a4 Mouse Activated Transient transfection, EMSA, Other Oatp2, Slc21a5 15
Abcc2 Mouse Activated Transient transfection, EMSA 17
Ugt1a1 Mouse Activated Transient transfection, EMSA 38
Sult2a1 Mouse Activated Transient transfection, EMSA 27
Abcb1b Mouse Activated Transient transfection, EMSA 11
Alas1 Mouse Activated Transient transfection, EMSA 10
Tissue Distribution Click here for help
Liver, intestine
Expression level:  High
Species:  Human
Technique:  Immunohistochemistry, Northern blot, Q-PCR
References:  2,4,16,18,20,39
Tissue Distribution Comments
Low levels in kidney and lungs. A similar pattern is seen in mice.
Physiological Consequences of Altering Gene Expression Click here for help
Increased bilirubin and cortisone clearance; increased detoxification of bile acids; increased protection against xenobiotic toxicants, such as zoxazolamine and tribromonoethanol
Species:  Mouse
Tissue: 
Technique:  Transgene of a constitutively activated hPXR into the liver of the transgenic mice
References:  36-38
Impaired drug metabolism induced by specific xenobiotics, such as loss of CYP3A11 inducibility in response to PCN and dexamethasone. Sensitivity to bile acid induced toxicity.
Species:  Mouse
Tissue: 
Technique:  Knock-out
References:  28,36-37
Acquired responsiveness to hPXR-specific ligands, such as refampicin; loss of responsiveness to rodent-specific ligands, such as PCN
Species:  Mouse
Tissue: 
Technique:  hPXR transgenic mice and hPXR transgenic with PXR KO background (“humanized” mice)
References:  36
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Nr1i2tm1Sakl Nr1i2tm1Sakl/Nr1i2tm1Sakl
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:1337040  MP:0005319 abnormal enzyme/ coenzyme level PMID: 11248085 
Nr1i2tm1Sakl Nr1i2tm1Sakl/Nr1i2tm1Sakl
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:1337040  MP:0008872 abnormal physiological response to xenobiotic PMID: 11248085 
Nr1i2tm1Sakl Nr1i2tm1Sakl/Nr1i2tm1Sakl
involves: 129S1/Sv * 129X1/SvJ		 MGI:1337040  MP:0004001 decreased hepatocyte proliferation PMID: 19815629 
Nr1i2tm1Rev Nr1i2tm1Rev/Nr1i2tm1Rev
involves: 129S4/SvJae * C57BL/6J		 MGI:1337040  MP:0008874 decreased physiological sensitivity to xenobiotic PMID: 10935643 
Nr1i2tm1Sakl Nr1i2tm1Sakl/Nr1i2tm1Sakl
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:1337040  MP:0008874 decreased physiological sensitivity to xenobiotic PMID: 11602523 
Nr1i2tm1(NR1I2)Arte Nr1i2tm1(NR1I2)Arte/Nr1i2tm1(NR1I2)Arte
involves: C57BL/6		 MGI:1337040  MP:0008874 decreased physiological sensitivity to xenobiotic PMID: 18677425 
Nr1i2tm3Arte Nr1i2tm3Arte/Nr1i2tm3Arte
involves: C57BL/6		 MGI:1337040  MP:0008874 decreased physiological sensitivity to xenobiotic PMID: 18677425 
Nr1i2tm3Arte|Nr1i3tm1.1Arte Nr1i2tm3Arte/Nr1i2tm3Arte,Nr1i3tm1.1Arte/Nr1i3tm1.1Arte
involves: C57BL/6		 MGI:1337040  MGI:1346307  MP:0008874 decreased physiological sensitivity to xenobiotic PMID: 18677425 
Nr1i2tm1(NR1I2)Arte|Nr1i3tm1.1Arte Nr1i2tm1(NR1I2)Arte/Nr1i2tm1(NR1I2)Arte,Nr1i3tm1.1Arte/Nr1i3tm1.1Arte
involves: C57BL/6		 MGI:1337040  MGI:1346307  MP:0008874 decreased physiological sensitivity to xenobiotic PMID: 18677425 
Nr1i2tm1Sakl Nr1i2tm1Sakl/Nr1i2tm1Sakl
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:1337040  MP:0009747 impaired behavioral response to xenobiotic PMID: 11248085 
Nr1i2tm1(NR1I2)Arte Nr1i2tm1(NR1I2)Arte/Nr1i2tm1(NR1I2)Arte
involves: C57BL/6		 MGI:1337040  MP:0008873 increased physiological sensitivity to xenobiotic PMID: 18677425 
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Breast cancer
Disease Ontology: DOID:1612
OMIM: 114480
Role:  Low PXR receptor level
Comments:  The levels of PXR mRNA in ER positive tumors were significantly lower that those observed in the ER negative tumors
References:  7
Disease:  Breast cancer
Disease Ontology: DOID:1612
OMIM: 114480
Role:  A significant positive correlation was detected between the SXR/hPXR labeling index and both the histologic grade and the lymph node status of the carcinoma cases
References:  21
Biologically Significant Variants Click here for help
Type:  Splice variant
Species:  Human
Description:  PXR3: has a different 5' UTR than variant 2. It encodes an isoform (3) that lacks 39 amino-terminal and 37 internal amino acids compared to isoform 2; the reading frame is maintained. Isoform 3 uses a non-AUG translation initiation codon.
Amino acids:  397
Nucleotide accession:  NM_033013
Protein accession:  NP_148934
Type:  Splice variant
Species:  Human
Description:  PXR2: Encoded by transcript variant 2 . This variant (2) has a different 5' UTR than other variants. It encodes a single full-length product (isoform 2) with an amino-terminal extension not found in other isoforms.
Amino acids:  473
Nucleotide accession:  NM_022002
Protein accession:  NP_071285
Type:  Splice variant
Species:  Human
Description:  PXR1: main isoform
Amino acids:  434
Nucleotide accession:  NM_003889
Protein accession:  NP_003880
References:  2,4,20

References

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1. Bartolini D, De Franco F, Torquato P, Marinelli R, Cerra B, Ronchetti R, Schon A, Fallarino F, De Luca A, Bellezza G et al.. (2020) Garcinoic Acid Is a Natural and Selective Agonist of Pregnane X Receptor. J Med Chem, 63 (7): 3701-3712. [PMID:32160459]

2. Bertilsson G, Heidrich J, Svensson K, Asman M, Jendeberg L, Sydow-Bäckman M, Ohlsson R, Postlind H, Blomquist P, Berkenstam A. (1998) Identification of a human nuclear receptor defines a new signaling pathway for CYP3A induction. Proc Natl Acad Sci USA, 95 (21): 12208-13. [PMID:9770465]

3. Bhalla S, Ozalp C, Fang S, Xiang L, Kemper JK. (2004) 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. J Biol Chem, 279 (43): 45139-47. [PMID:15322103]

4. Blumberg B, Sabbagh W, Juguilon H, Bolado J, van Meter CM, Ong ES, Evans RM. (1998) SXR, a novel steroid and xenobiotic-sensing nuclear receptor. Genes Dev, 12 (20): 3195-205. [PMID:9784494]

5. Cavaillès V, Dauvois S, L'Horset F, Lopez G, Hoare S, Kushner PJ, Parker MG. (1995) Nuclear factor RIP140 modulates transcriptional activation by the estrogen receptor. EMBO J, 14 (15): 3741-51. [PMID:7641693]

6. Chen Y, Kissling G, Negishi M, Goldstein JA. (2005) The nuclear receptors constitutive androstane receptor and pregnane X receptor cross-talk with hepatic nuclear factor 4alpha to synergistically activate the human CYP2C9 promoter. J Pharmacol Exp Ther, 314 (3): 1125-33. [PMID:15919766]

7. Dotzlaw H, Leygue E, Watson P, Murphy LC. (1999) The human orphan receptor PXR messenger RNA is expressed in both normal and neoplastic breast tissue. Clin Cancer Res, 5 (8): 2103-7. [PMID:10473093]

8. Dussault I, Yoo HD, Lin M, Wang E, Fan M, Batta AK, Salen G, Erickson SK, Forman BM. (2003) Identification of an endogenous ligand that activates pregnane X receptor-mediated sterol clearance. Proc Natl Acad Sci USA, 100 (3): 833-8. [PMID:12569201]

9. Ferguson SS, Chen Y, LeCluyse EL, Negishi M, Goldstein JA. (2005) Human CYP2C8 is transcriptionally regulated by the nuclear receptors constitutive androstane receptor, pregnane X receptor, glucocorticoid receptor, and hepatic nuclear factor 4alpha. Mol Pharmacol, 68 (3): 747-57. [PMID:15933212]

10. Fraser DJ, Zumsteg A, Meyer UA. (2003) Nuclear receptors constitutive androstane receptor and pregnane X receptor activate a drug-responsive enhancer of the murine 5-aminolevulinic acid synthase gene. J Biol Chem, 278 (41): 39392-401. [PMID:12881517]

11. Geick A, Eichelbaum M, Burk O. (2001) Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin. J Biol Chem, 276 (18): 14581-7. [PMID:11297522]

12. Gonzalez MM, Carlberg C. (2002) Cross-repression, a functional consequence of the physical interaction of non-liganded nuclear receptors and POU domain transcription factors. J Biol Chem, 277 (21): 18501-9. [PMID:11891224]

13. Goodwin B, Gauthier KC, Umetani M, Watson MA, Lochansky MI, Collins JL, Leitersdorf E, Mangelsdorf DJ, Kliewer SA, Repa JJ. (2003) Identification of bile acid precursors as endogenous ligands for the nuclear xenobiotic pregnane X receptor. Proc Natl Acad Sci USA, 100 (1): 223-8. [PMID:12509506]

14. Goodwin B, Moore LB, Stoltz CM, McKee DD, Kliewer SA. (2001) Regulation of the human CYP2B6 gene by the nuclear pregnane X receptor. Mol Pharmacol, 60 (3): 427-31. [PMID:11502872]

15. Guo GL, Staudinger J, Ogura K, Klaassen CD. (2002) Induction of rat organic anion transporting polypeptide 2 by pregnenolone-16alpha-carbonitrile is via interaction with pregnane X receptor. Mol Pharmacol, 61 (4): 832-9. [PMID:11901222]

16. Jones SA, Moore LB, Shenk JL, Wisely GB, Hamilton GA, McKee DD, Tomkinson NC, LeCluyse EL, Lambert MH, Willson TM, Kliewer SA, Moore JT. (2000) The pregnane X receptor: a promiscuous xenobiotic receptor that has diverged during evolution. Mol Endocrinol, 14 (1): 27-39. [PMID:10628745]

17. Kast HR, Goodwin B, Tarr PT, Jones SA, Anisfeld AM, Stoltz CM, Tontonoz P, Kliewer S, Willson TM, Edwards PA. (2002) Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and constitutive androstane receptor. J Biol Chem, 277 (4): 2908-15. [PMID:11706036]

18. Kliewer SA, Moore JT, Wade L, Staudinger JL, Watson MA, Jones SA, McKee DD, Oliver BB, Willson TM, Zetterström RH, Perlmann T, Lehmann JM. (1998) An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell, 92 (1): 73-82. [PMID:9489701]

19. Kodama S, Koike C, Negishi M, Yamamoto Y. (2004) Nuclear receptors CAR and PXR cross talk with FOXO1 to regulate genes that encode drug-metabolizing and gluconeogenic enzymes. Mol Cell Biol, 24 (18): 7931-40. [PMID:15340055]

20. Lehmann JM, McKee DD, Watson MA, Willson TM, Moore JT, Kliewer SA. (1998) The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions. J Clin Invest, 102 (5): 1016-23. [PMID:9727070]

21. Miki Y, Suzuki T, Kitada K, Yabuki N, Shibuya R, Moriya T, Ishida T, Ohuchi N, Blumberg B, Sasano H. (2006) Expression of the steroid and xenobiotic receptor and its possible target gene, organic anion transporting polypeptide-A, in human breast carcinoma. Cancer Res, 66 (1): 535-42. [PMID:16397270]

22. Moore LB, Goodwin B, Jones SA, Wisely GB, Serabjit-Singh CJ, Willson TM, Collins JL, Kliewer SA. (2000) St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proc Natl Acad Sci USA, 97 (13): 7500-2. [PMID:10852961]

23. Mu Y, Stephenson CR, Kendall C, Saini SP, Toma D, Ren S, Cai H, Strom SC, Day BW, Wipf P, Xie W. (2005) A pregnane X receptor agonist with unique species-dependent stereoselectivity and its implications in drug development. Mol Pharmacol, 68 (2): 403-13. [PMID:15872116]

24. Mu Y, Zhang J, Zhang S, Zhou HH, Toma D, Ren S, Huang L, Yaramus M, Baum A, Venkataramanan R, Xie W. (2006) Traditional Chinese medicines Wu Wei Zi (Schisandra chinensis Baill) and Gan Cao (Glycyrrhiza uralensis Fisch) activate pregnane X receptor and increase warfarin clearance in rats. J Pharmacol Exp Ther, 316 (3): 1369-77. [PMID:16267138]

25. Ourlin JC, Lasserre F, Pineau T, Fabre JM, Sa-Cunha A, Maurel P, Vilarem MJ, Pascussi JM. (2003) The small heterodimer partner interacts with the pregnane X receptor and represses its transcriptional activity. Mol Endocrinol, 17 (9): 1693-703. [PMID:12805410]

26. Schuetz EG, Brimer C, Schuetz JD. (1998) Environmental xenobiotics and the antihormones cyproterone acetate and spironolactone use the nuclear hormone pregnenolone X receptor to activate the CYP3A23 hormone response element. Mol Pharmacol, 54 (6): 1113-7. [PMID:9855641]

27. Sonoda J, Xie W, Rosenfeld JM, Barwick JL, Guzelian PS, Evans RM. (2002) Regulation of a xenobiotic sulfonation cascade by nuclear pregnane X receptor (PXR). Proc Natl Acad Sci USA, 99 (21): 13801-6. [PMID:12370413]

28. Staudinger JL, Goodwin B, Jones SA, Hawkins-Brown D, MacKenzie KI, LaTour A, Liu Y, Klaassen CD, Brown KK, Reinhard J, Willson TM, Koller BH, Kliewer SA. (2001) The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc Natl Acad Sci USA, 98 (6): 3369-74. [PMID:11248085]

29. Sugatani J, Nishitani S, Yamakawa K, Yoshinari K, Sueyoshi T, Negishi M, Miwa M. (2005) Transcriptional regulation of human UGT1A1 gene expression: activated glucocorticoid receptor enhances constitutive androstane receptor/pregnane X receptor-mediated UDP-glucuronosyltransferase 1A1 regulation with glucocorticoid receptor-interacting protein 1. Mol Pharmacol, 67 (3): 845-55. [PMID:15557560]

30. Synold TW, Dussault I, Forman BM. (2001) The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux. Nat Med, 7 (5): 584-90. [PMID:11329060]

31. Tabb MM, Sun A, Zhou C, Grün F, Errandi J, Romero K, Pham H, Inoue S, Mallick S, Lin M, Forman BM, Blumberg B. (2003) Vitamin K2 regulation of bone homeostasis is mediated by the steroid and xenobiotic receptor SXR. J Biol Chem, 278 (45): 43919-27. [PMID:12920130]

32. Takeshita A, Taguchi M, Koibuchi N, Ozawa Y. (2002) Putative role of the orphan nuclear receptor SXR (steroid and xenobiotic receptor) in the mechanism of CYP3A4 inhibition by xenobiotics. J Biol Chem, 277 (36): 32453-8. [PMID:12072427]

33. Wang W, Prosise WW, Chen J, Taremi SS, Le HV, Madison V, Cui X, Thomas A, Cheng KC, Lesburg CA. (2008) Construction and characterization of a fully active PXR/SRC-1 tethered protein with increased stability. Protein Eng Des Sel, 21 (7): 425-33. [PMID:18456871]

34. Wentworth JM, Agostini M, Love J, Schwabe JW, Chatterjee VK. (2000) St John's wort, a herbal antidepressant, activates the steroid X receptor. J Endocrinol, 166 (3): R11-6. [PMID:10974665]

35. Wyde ME, Bartolucci E, Ueda A, Zhang H, Yan B, Negishi M, You L. (2003) The environmental pollutant 1,1-dichloro-2,2-bis (p-chlorophenyl)ethylene induces rat hepatic cytochrome P450 2B and 3A expression through the constitutive androstane receptor and pregnane X receptor. Mol Pharmacol, 64 (2): 474-81. [PMID:12869653]

36. Xie W, Barwick JL, Downes M, Blumberg B, Simon CM, Nelson MC, Neuschwander-Tetri BA, Brunt EM, Guzelian PS, Evans RM. (2000) Humanized xenobiotic response in mice expressing nuclear receptor SXR. Nature, 406 (6794): 435-9. [PMID:10935643]

37. Xie W, Radominska-Pandya A, Shi Y, Simon CM, Nelson MC, Ong ES, Waxman DJ, Evans RM. (2001) An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids. Proc Natl Acad Sci USA, 98 (6): 3375-80. [PMID:11248086]

38. Xie W, Yeuh MF, Radominska-Pandya A, Saini SP, Negishi Y, Bottroff BS, Cabrera GY, Tukey RH, Evans RM. (2003) Control of steroid, heme, and carcinogen metabolism by nuclear pregnane X receptor and constitutive androstane receptor. Proc Natl Acad Sci USA, 100 (7): 4150-5. [PMID:12644700]

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