Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7UVICX)

DOT Name Nuclear receptor subfamily 0 group B member 2 (NR0B2)
Synonyms Orphan nuclear receptor SHP; Small heterodimer partner
Gene Name NR0B2
Related Disease
Schizophrenia ( )
UniProt ID
NR0B2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1YUC; 2Q3Y; 2Z4J; 4DOR; 4ONI; 5UFS; 6W9M; 7YXC; 7YXD; 7YXN; 7YXO; 7YXP; 7YXR
Pfam ID
PF00104
Sequence
MSTSQPGACPCQGAASRPAILYALLSSSLKAVPRPRSRCLCRQHRPVQLCAPHRTCREAL
DVLAKTVAFLRNLPSFWQLPPQDQRRLLQGCWGPLFLLGLAQDAVTFEVAEAPVPSILKK
ILLEEPSSSGGSGQLPDRPQPSLAAVQWLQCCLESFWSLELSPKEYACLKGTILFNPDVP
GLQAASHIGHLQQEAHWVLCEVLEPWCPAAQGRLTRVLLTASTLKSIPTSLLGDLFFRPI
IGDVDIAGLLGDMLLLR
Function
Transcriptional regulator that acts as a negative regulator of receptor-dependent signaling pathways. Specifically inhibits transactivation of the nuclear receptor with which it interacts. Inhibits transcriptional activity of NEUROD1 on E-box-containing promoter by interfering with the coactivation function of the p300/CBP-mediated transcription complex for NEUROD1. Essential component of the liver circadian clock which via its interaction with NR1D1 and RORG regulates NPAS2-mediated hepatic lipid metabolism. Regulates the circadian expression of cytochrome P450 (CYP) enzymes. Represses: NR5A2 and HNF4A to down-regulate CYP2C38, NFLI3 to up-regulate CYP2A5, BHLHE41/HNF1A axis to up-regulate CYP1A2, CYP2E1 and CYP3A11, and NR1D1 to up-regulate CYP2B10, CYP4A10 and CYP4A14.
Tissue Specificity Liver. Low levels of expression were detected in heart and pancreas.
KEGG Pathway
Bile secretion (hsa04976 )
Reactome Pathway
Nuclear Receptor transcription pathway (R-HSA-383280 )

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Schizophrenia DISSRV2N No Known Unknown [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
62 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [2]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [3]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [4]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [5]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [6]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [7]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [8]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [9]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [10]
Menadione DMSJDTY Approved Menadione affects the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [8]
Fulvestrant DM0YZC6 Approved Fulvestrant decreases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [6]
Diclofenac DMPIHLS Approved Diclofenac affects the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [10]
Clozapine DMFC71L Approved Clozapine increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [11]
Obeticholic acid DM3Q1SM Approved Obeticholic acid increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [12]
Fenofibrate DMFKXDY Approved Fenofibrate increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [13]
Rifampicin DM5DSFZ Approved Rifampicin decreases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [14]
Haloperidol DM96SE0 Approved Haloperidol increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [2]
Ursodeoxycholic acid DMCUT21 Approved Ursodeoxycholic acid increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [15]
Fluoxetine DM3PD2C Approved Fluoxetine increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [11]
Imatinib DM7RJXL Approved Imatinib increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [16]
Sertraline DM0FB1J Approved Sertraline increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [11]
Bexarotene DMOBIKY Approved Bexarotene increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [17]
Chenodiol DMQ8JIK Approved Chenodiol increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [18]
Deoxycholic acid DM3GYAL Approved Deoxycholic acid increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [19]
Clavulanate DM2FGRT Approved Clavulanate increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [20]
Thioridazine DM35M8J Approved Thioridazine increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [2]
Imipramine DM2NUH3 Approved Imipramine increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [11]
Clomipramine DMINRKW Approved Clomipramine increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [2]
Methoxsalen DME8FZ9 Approved Methoxsalen increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [21]
Loratadine DMF3AN7 Approved Loratadine increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [11]
Pentamidine DMHZJCG Approved Pentamidine increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [11]
Flecainide DMSQDLE Approved Flecainide increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [2]
Cholic acid DM7OKQV Approved Cholic acid increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [22]
Perhexiline DMINO7Z Approved Perhexiline increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [11]
Calcipotriol DM03CP7 Approved Calcipotriol increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [21]
Disopyramide DM5SYZP Approved Disopyramide decreases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [11]
Sumatriptan DMVYXR8 Approved Sumatriptan decreases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [11]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [23]
Resveratrol DM3RWXL Phase 3 Resveratrol increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [24]
Epigallocatechin gallate DMCGWBJ Phase 3 Epigallocatechin gallate increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [25]
Chlorpromazine DMBGZI3 Phase 3 Trial Chlorpromazine increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [2]
Phenol DM1QSM3 Phase 2/3 Phenol decreases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [26]
PD-0325901 DM27D4J Phase 2 PD-0325901 decreases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [27]
Taurocholic acid DM2LZ8F Phase 1/2 Taurocholic acid increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [15]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [28]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [29]
Chlorcyclizine DM3L52Q Phase 1 Chlorcyclizine increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [11]
PX-102 DMWU682 Phase 1 PX-102 increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [30]
ZIMELIDINE DMNI3U2 Withdrawn from market ZIMELIDINE increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [2]
Nickel chloride DMI12Y8 Investigative Nickel chloride decreases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [26]
Resorcinol DMM37C0 Investigative Resorcinol increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [31]
U0126 DM31OGF Investigative U0126 decreases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [27]
Oleic acid DM54O1Z Investigative Oleic acid decreases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [32]
DM9CEI5 increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [33]
GW7647 DM9RD0C Investigative GW7647 decreases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [32]
Farnesol DMV2X1B Investigative Farnesol decreases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [32]
GW-3965 DMG60ET Investigative GW-3965 increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [17]
Icariside II DM3DB8X Investigative Icariside II decreases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [34]
Ginsenoside Re DM46FVD Investigative Ginsenoside Re increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [35]
CI-1040 DMF3DZX Investigative CI-1040 decreases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [27]
paxilline DMPF2N1 Investigative paxilline increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [17]
CD3254 DM38MU1 Investigative CD3254 increases the expression of Nuclear receptor subfamily 0 group B member 2 (NR0B2). [17]
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⏷ Show the Full List of 62 Drug(s)

References

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2 Determination of phospholipidosis potential based on gene expression analysis in HepG2 cells. Toxicol Sci. 2007 Mar;96(1):101-14.
3 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
4 Combination of retinoic acid and ursodeoxycholic acid attenuates liver injury in bile duct-ligated rats and human hepatic cells. Hepatology. 2011 Feb;53(2):548-57. doi: 10.1002/hep.24047. Epub 2010 Dec 10.
5 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
6 Arsenite and cadmium promote the development of mammary tumors. Carcinogenesis. 2020 Jul 14;41(7):1005-1014. doi: 10.1093/carcin/bgz176.
7 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
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9 Primary Human Hepatocyte Spheroids as Tools to Study the Hepatotoxic Potential of Non-Pharmaceutical Chemicals. Int J Mol Sci. 2021 Oct 12;22(20):11005. doi: 10.3390/ijms222011005.
10 Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
11 A toxicogenomic approach to drug-induced phospholipidosis: analysis of its induction mechanism and establishment of a novel in vitro screening system. Toxicol Sci. 2005 Feb;83(2):282-92.
12 The methyl transferase PRMT1 functions as co-activator of farnesoid X receptor (FXR)/9-cis retinoid X receptor and regulates transcription of FXR responsive genes. Mol Pharmacol. 2005 Aug;68(2):551-8. doi: 10.1124/mol.105.012104. Epub 2005 May 23.
13 Fenofibrate differentially regulates plasminogen activator inhibitor-1 gene expression via adenosine monophosphate-activated protein kinase-dependent induction of orphan nuclear receptor small heterodimer partner. Hepatology. 2009 Sep;50(3):880-92. doi: 10.1002/hep.23049.
14 Expression dynamics of pregnane X receptor-controlled genes in 3D primary human hepatocyte spheroids. Arch Toxicol. 2022 Jan;96(1):195-210. doi: 10.1007/s00204-021-03177-y. Epub 2021 Oct 23.
15 Role of vitamin C transporters and biliverdin reductase in the dual pro-oxidant and anti-oxidant effect of biliary compounds on the placental-fetal unit in cholestasis during pregnancy. Toxicol Appl Pharmacol. 2008 Oct 15;232(2):327-36.
16 Investigation of imatinib and other approved drugs as starting points for antidiabetic drug discovery with FXR modulating activity. Biochem Pharmacol. 2012 Jun 15;83(12):1674-81. doi: 10.1016/j.bcp.2012.02.027. Epub 2012 Mar 7.
17 Combinations of LXR and RXR agonists induce triglyceride accumulation in human HepaRG cells in a synergistic manner. Arch Toxicol. 2020 Apr;94(4):1303-1320. doi: 10.1007/s00204-020-02685-7. Epub 2020 Mar 2.
18 VPAC1 expression is regulated by FXR agonists in the human gallbladder epithelium. Hepatology. 2005 Sep;42(3):549-57. doi: 10.1002/hep.20806.
19 Farnesoid X receptor induces murine scavenger receptor Class B type I via intron binding. PLoS One. 2012;7(4):e35895. doi: 10.1371/journal.pone.0035895. Epub 2012 Apr 23.
20 Molecular mechanisms of hepatotoxic cholestasis by clavulanic acid: Role of NRF2 and FXR pathways. Food Chem Toxicol. 2021 Dec;158:112664. doi: 10.1016/j.fct.2021.112664. Epub 2021 Nov 9.
21 Adaptive homeostasis of the vitamin D-vitamin D nuclear receptor axis in 8-methoxypsoralen-induced hepatotoxicity. Toxicol Appl Pharmacol. 2019 Jan 1;362:150-158. doi: 10.1016/j.taap.2018.11.002. Epub 2018 Nov 10.
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23 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
24 Structural modification of resveratrol leads to increased anti-tumor activity, but causes profound changes in the mode of action. Toxicol Appl Pharmacol. 2015 Aug 15;287(1):67-76. doi: 10.1016/j.taap.2015.05.020. Epub 2015 Jun 2.
25 A tea catechin, epigallocatechin-3-gallate, is a unique modulator of the farnesoid X receptor. Toxicol Appl Pharmacol. 2012 Jan 15;258(2):268-74. doi: 10.1016/j.taap.2011.11.006. Epub 2011 Dec 4.
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27 U0126, a mitogen-activated protein kinase kinase 1 and 2 (MEK1 and 2) inhibitor, selectively up-regulates main isoforms of CYP3A subfamily via a pregnane X receptor (PXR) in HepG2 cells. Arch Toxicol. 2014 Dec;88(12):2243-59.
28 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
29 CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
30 Farnesoid X receptor (FXR) agonists induce hepatocellular apoptosis and impair hepatic functions via FXR/SHP pathway. Arch Toxicol. 2022 Jun;96(6):1829-1843. doi: 10.1007/s00204-022-03266-6. Epub 2022 Mar 10.
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32 Farnesol induces fatty acid oxidation and decreases triglyceride accumulation in steatotic HepaRG cells. Toxicol Appl Pharmacol. 2019 Feb 15;365:61-70.
33 Expression and regulation of the bile acid transporter, OSTalpha-OSTbeta in rat and human intestine and liver. Biopharm Drug Dispos. 2009 Jul;30(5):241-58.
34 Baohuoside I inhibits FXR signaling pathway to interfere with bile acid homeostasis via targeting ER degradation. Cell Biol Toxicol. 2023 Aug;39(4):1215-1235. doi: 10.1007/s10565-022-09737-x. Epub 2022 Jul 8.
35 Ginsenoside Re lowers blood glucose and lipid levels via activation of AMP-activated protein kinase in HepG2 cells and high-fat diet fed mice. Int J Mol Med. 2012 Jan;29(1):73-80. doi: 10.3892/ijmm.2011.805. Epub 2011 Oct 3.