Details of Drug Off-Target (DOT)

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

DOT Name Bile acid receptor (NR1H4)
Synonyms Farnesoid X-activated receptor; Farnesol receptor HRR-1; Nuclear receptor subfamily 1 group H member 4; Retinoid X receptor-interacting protein 14; RXR-interacting protein 14
Gene Name NR1H4
Related Disease
Cholestasis, progressive familial intrahepatic, 5 ( )
UniProt ID
NR1H4_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1OSH ; 3BEJ ; 3DCT ; 3DCU ; 3FLI ; 3FXV ; 3GD2 ; 3HC5 ; 3HC6 ; 3L1B ; 3OKH ; 3OKI ; 3OLF ; 3OMK ; 3OMM ; 3OOF ; 3OOK ; 3P88 ; 3P89 ; 3RUT ; 3RUU ; 3RVF ; 4OIV ; 4QE8 ; 4WVD ; 5IAW ; 5ICK ; 5Q0I ; 5Q0J ; 5Q0K ; 5Q0L ; 5Q0M ; 5Q0N ; 5Q0O ; 5Q0P ; 5Q0Q ; 5Q0R ; 5Q0S ; 5Q0T ; 5Q0U ; 5Q0V ; 5Q0W ; 5Q0X ; 5Q0Y ; 5Q0Z ; 5Q10 ; 5Q11 ; 5Q12 ; 5Q13 ; 5Q14 ; 5Q15 ; 5Q16 ; 5Q17 ; 5Q18 ; 5Q19 ; 5Q1A ; 5Q1B ; 5Q1C ; 5Q1D ; 5Q1E ; 5Q1F ; 5Q1G ; 5Q1H ; 5Q1I ; 5WZX ; 5Y1J ; 5Y44 ; 5Y49 ; 5YXB ; 5YXD ; 5YXJ ; 5YXL ; 5Z12 ; 6A5W ; 6A5X ; 6A5Y ; 6A5Z ; 6A60 ; 6HL0 ; 6HL1 ; 6ITM ; 7D42 ; 7TRB ; 7VUE ; 8HBM ; 8HD3
Pfam ID
PF00104 ; PF00105
Sequence
MVMQFQGLENPIQISPHCSCTPSGFFMEMMSMKPAKGVLTEQVAGPLGQNLEVEPYSQYS
NVQFPQVQPQISSSSYYSNLGFYPQQPEEWYSPGIYELRRMPAETLYQGETEVAEMPVTK
KPRMGASAGRIKGDELCVVCGDRASGYHYNALTCEGCKGFFRRSITKNAVYKCKNGGNCV
MDMYMRRKCQECRLRKCKEMGMLAECMYTGLLTEIQCKSKRLRKNVKQHADQTVNEDSEG
RDLRQVTSTTKSCREKTELTPDQQTLLHFIMDSYNKQRMPQEITNKILKEEFSAEENFLI
LTEMATNHVQVLVEFTKKLPGFQTLDHEDQIALLKGSAVEAMFLRSAEIFNKKLPSGHSD
LLEERIRNSGISDEYITPMFSFYKSIGELKMTQEEYALLTAIVILSPDRQYIKDREAVEK
LQEPLLDVLQKLCKIHQPENPQHFACLLGRLTELRTFNHHHAEMLMSWRVNDHKFTPLLC
EIWDVQ
Function
Ligand-activated transcription factor. Receptor for bile acids (BAs) such as chenodeoxycholic acid (CDCA), lithocholic acid, deoxycholic acid (DCA) and allocholic acid (ACA). Plays a essential role in BA homeostasis through the regulation of genes involved in BA synthesis, conjugation and enterohepatic circulation. Also regulates lipid and glucose homeostasis and is involved innate immune response. The FXR-RXR heterodimer binds predominantly to farnesoid X receptor response elements (FXREs) containing two inverted repeats of the consensus sequence 5'-AGGTCA-3' in which the monomers are spaced by 1 nucleotide (IR-1) but also to tandem repeat DR1 sites with lower affinity, and can be activated by either FXR or RXR-specific ligands. It is proposed that monomeric nuclear receptors such as NR5A2/LRH-1 bound to coregulatory nuclear responsive element (NRE) halfsites located in close proximity to FXREs modulate transcriptional activity. In the liver activates transcription of the corepressor NR0B2 thereby indirectly inhibiting CYP7A1 and CYP8B1 (involved in BA synthesis) implicating at least in part histone demethylase KDM1A resulting in epigenomic repression, and SLC10A1/NTCP (involved in hepatic uptake of conjugated BAs). Activates transcription of the repressor MAFG (involved in regulation of BA synthesis). Activates transcription of SLC27A5/BACS and BAAT (involved in BA conjugation), ABCB11/BSEP (involved in bile salt export) by directly recruiting histone methyltransferase CARM1, and ABCC2/MRP2 (involved in secretion of conjugated BAs) and ABCB4 (involved in secretion of phosphatidylcholine in the small intestine). Activates transcription of SLC27A5/BACS and BAAT (involved in BA conjugation), ABCB11/BSEP (involved in bile salt export) by directly recruiting histone methyltransferase CARM1, and ABCC2/MRP2 (involved in secretion of conjugated BAs) and ABCB4 (involved in secretion of phosphatidylcholine in the small intestine). In the intestine activates FGF19 expression and secretion leading to hepatic CYP7A1 repression. The function also involves the coordinated induction of hepatic KLB/beta-klotho expression. Regulates transcription of liver UGT2B4 and SULT2A1 involved in BA detoxification; binding to the UGT2B4 promoter seems to imply a monomeric transactivation independent of RXRA. Modulates lipid homeostasis by activating liver NR0B2/SHP-mediated repression of SREBF1 (involved in de novo lipogenesis), expression of PLTP (involved in HDL formation), SCARB1 (involved in HDL hepatic uptake), APOE, APOC1, APOC4, PPARA (involved in beta-oxidation of fatty acids), VLDLR and SDC1 (involved in the hepatic uptake of LDL and IDL remnants), and inhibiting expression of MTTP (involved in VLDL assembly. Increases expression of APOC2 (promoting lipoprotein lipase activity implicated in triglyceride clearance). Transrepresses APOA1 involving a monomeric competition with NR2A1 for binding to a DR1 element. Also reduces triglyceride clearance by inhibiting expression of ANGPTL3 and APOC3 (both involved in inhibition of lipoprotein lipase). Involved in glucose homeostasis by modulating hepatic gluconeogenesis through activation of NR0B2/SHP-mediated repression of respective genes. Modulates glycogen synthesis (inducing phosphorylation of glycogen synthase kinase-3). Modulates glucose-stimulated insulin secretion and is involved in insulin resistance. Involved in intestinal innate immunity. Plays a role in protecting the distal small intestine against bacterial overgrowth and preservation of the epithelial barrier. Down-regulates inflammatory cytokine expression in several types of immune cells including macrophages and mononuclear cells. Mediates trans-repression of TLR4-induced cytokine expression; the function seems to require its sumoylation and prevents N-CoR nuclear receptor corepressor clearance from target genes such as IL1B and NOS2. Involved in the TLR9-mediated protective mechanism in intestinal inflammation. Plays an anti-inflammatory role in liver inflammation; proposed to inhibit pro-inflammatory (but not antiapoptotic) NF-kappa-B signaling); [Isoform 1]: Promotes transcriptional activation of target genes NR0B2/SHP (inducible by unconjugated CDCA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and FABP6/IBAP; low activity for ABCB11/BSEP (inducible by unconjugated CDCA, DCA and ACA); not inducible by taurine- and glycine-amidated CDCA; [Isoform 2]: Promotes transcriptional activation of target genes ABCB11/BSEP (inducible by unconjugated CDCA, DCA and ACA), NR0B2/SHP (inducible by unconjugated CDCA DCA and ACA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and FABP6/IBAP; not inducible by taurine- and glycine-amidated CDCA; [Isoform 3]: Promotes transcriptional activation of target genes NR0B2/SHP (inducible by unconjugated CDCA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and IBAP; low activity for ABCB11/BSEP (inducible by unconjugated CDCA, DCA and ACA); not inducible by taurine- and glycine-amidated CDCA; [Isoform 4]: Promotes transcriptional activation of target genes ABCB11/BSEP (inducible by unconjugated CDCA, ACA and DCA), NR0B2/SHP (inducible by unconjugated CDCA, ACA and DCA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and FABP6/IBAP; most efficient isoform compared to isoforms 1 to 3; not inducible by taurine- and glycine-amidated CDCA.
Tissue Specificity
Liver and hepatocyte-related cells express mainly FXRalpha1-type isoforms with isoform 3 and isoform 4 in approximately equal proportions. In intestine and kidney mainly FXRalpha2-type isoforms are expressed with isoform 1 and isoform 2 in approximately equal proportions. Expressed in pancreatic beta cells and macrophages.
KEGG Pathway
Bile secretion (hsa04976 )
Reactome Pathway
(Name not found )
Synthesis of bile acids and bile salts (R-HSA-192105 )
Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol (R-HSA-193368 )
Synthesis of bile acids and bile salts via 27-hydroxycholesterol (R-HSA-193807 )
PPARA activates gene expression (R-HSA-1989781 )
Endogenous sterols (R-HSA-211976 )
Nuclear Receptor transcription pathway (R-HSA-383280 )
Recycling of bile acids and salts (R-HSA-159418 )

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Cholestasis, progressive familial intrahepatic, 5 DIS7KNN7 Strong Autosomal recessive [1]
------------------------------------------------------------------------------------
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
63 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of Bile acid receptor (NR1H4). [2]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Bile acid receptor (NR1H4). [3]
Tretinoin DM49DUI Approved Tretinoin increases the activity of Bile acid receptor (NR1H4). [4]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Bile acid receptor (NR1H4). [5]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the activity of Bile acid receptor (NR1H4). [6]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Bile acid receptor (NR1H4). [7]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Bile acid receptor (NR1H4). [8]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Bile acid receptor (NR1H4). [3]
Ivermectin DMDBX5F Approved Ivermectin increases the expression of Bile acid receptor (NR1H4). [9]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Bile acid receptor (NR1H4). [10]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Bile acid receptor (NR1H4). [11]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Bile acid receptor (NR1H4). [12]
Triclosan DMZUR4N Approved Triclosan increases the expression of Bile acid receptor (NR1H4). [13]
Zoledronate DMIXC7G Approved Zoledronate decreases the expression of Bile acid receptor (NR1H4). [14]
Menadione DMSJDTY Approved Menadione affects the expression of Bile acid receptor (NR1H4). [12]
Ethanol DMDRQZU Approved Ethanol decreases the expression of Bile acid receptor (NR1H4). [15]
Ethinyl estradiol DMODJ40 Approved Ethinyl estradiol decreases the expression of Bile acid receptor (NR1H4). [17]
Daunorubicin DMQUSBT Approved Daunorubicin decreases the activity of Bile acid receptor (NR1H4). [6]
Lindane DMB8CNL Approved Lindane increases the expression of Bile acid receptor (NR1H4). [18]
Ursodeoxycholic acid DMCUT21 Approved Ursodeoxycholic acid decreases the expression of Bile acid receptor (NR1H4). [19]
Imatinib DM7RJXL Approved Imatinib increases the activity of Bile acid receptor (NR1H4). [20]
Ritonavir DMU764S Approved Ritonavir increases the expression of Bile acid receptor (NR1H4). [21]
Nefazodone DM4ZS8M Approved Nefazodone decreases the expression of Bile acid receptor (NR1H4). [22]
Dihydroartemisinin DMBXVMZ Approved Dihydroartemisinin increases the expression of Bile acid receptor (NR1H4). [15]
Bosentan DMIOGBU Approved Bosentan decreases the expression of Bile acid receptor (NR1H4). [23]
Deoxycholic acid DM3GYAL Approved Deoxycholic acid increases the expression of Bile acid receptor (NR1H4). [24]
Atazanavir DMSYRBX Approved Atazanavir decreases the expression of Bile acid receptor (NR1H4). [22]
Nifedipine DMSVOZT Approved Nifedipine decreases the activity of Bile acid receptor (NR1H4). [6]
Pentamidine DMHZJCG Approved Pentamidine increases the activity of Bile acid receptor (NR1H4). [20]
Dobutamine DMD1B8Z Approved Dobutamine increases the activity of Bile acid receptor (NR1H4). [20]
Cholic acid DM7OKQV Approved Cholic acid increases the expression of Bile acid receptor (NR1H4). [24]
Felodipine DMOSW35 Approved Felodipine increases the activity of Bile acid receptor (NR1H4). [6]
Idarubicin DMM0XGL Approved Idarubicin decreases the activity of Bile acid receptor (NR1H4). [6]
Nimodipine DMQ0RKZ Approved Nimodipine decreases the activity of Bile acid receptor (NR1H4). [6]
Nitrendipine DM21C09 Approved Nitrendipine increases the activity of Bile acid receptor (NR1H4). [6]
Nisoldipine DM7ISKJ Approved Nisoldipine decreases the activity of Bile acid receptor (NR1H4). [6]
Papaverine DMCA9QP Approved Papaverine increases the activity of Bile acid receptor (NR1H4). [20]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Bile acid receptor (NR1H4). [26]
Benidipine DMWNP6B Phase 4 Benidipine decreases the activity of Bile acid receptor (NR1H4). [6]
Lacidipine DMQP5I3 Phase 4 Lacidipine increases the activity of Bile acid receptor (NR1H4). [6]
Tamibarotene DM3G74J Phase 3 Tamibarotene increases the activity of Bile acid receptor (NR1H4). [6]
Epigallocatechin gallate DMCGWBJ Phase 3 Epigallocatechin gallate increases the activity of Bile acid receptor (NR1H4). [27]
Manidipine DMJPGUA Phase 3 Manidipine increases the activity of Bile acid receptor (NR1H4). [6]
Cilnidipine DM1975O Phase 3 Cilnidipine increases the activity of Bile acid receptor (NR1H4). [6]
OTX-015 DMI8RG1 Phase 1/2 OTX-015 decreases the expression of Bile acid receptor (NR1H4). [28]
Taurocholic acid DM2LZ8F Phase 1/2 Taurocholic acid increases the expression of Bile acid receptor (NR1H4). [29]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Bile acid receptor (NR1H4). [28]
Mivebresib DMCPF90 Phase 1 Mivebresib decreases the expression of Bile acid receptor (NR1H4). [28]
PMID27336223-Compound-5 DM6E50A Patented PMID27336223-Compound-5 increases the activity of Bile acid receptor (NR1H4). [6]
LG100268 DM41RK2 Discontinued in Phase 1 LG100268 decreases the activity of Bile acid receptor (NR1H4). [31]
Nemorubicin DMX7Q3H Preclinical Nemorubicin decreases the activity of Bile acid receptor (NR1H4). [6]
Acetaldehyde DMJFKG4 Investigative Acetaldehyde decreases the expression of Bile acid receptor (NR1H4). [32]
Paraquat DMR8O3X Investigative Paraquat increases the expression of Bile acid receptor (NR1H4). [13]
Hexadecanoic acid DMWUXDZ Investigative Hexadecanoic acid increases the expression of Bile acid receptor (NR1H4). [9]
D-glucose DMMG2TO Investigative D-glucose affects the expression of Bile acid receptor (NR1H4). [33]
Oleic acid DM54O1Z Investigative Oleic acid decreases the expression of Bile acid receptor (NR1H4). [34]
GW7647 DM9RD0C Investigative GW7647 decreases the expression of Bile acid receptor (NR1H4). [34]
Farnesol DMV2X1B Investigative Farnesol decreases the expression of Bile acid receptor (NR1H4). [34]
Chlorogenic acid DM2Y3P4 Investigative Chlorogenic acid increases the expression of Bile acid receptor (NR1H4). [35]
Icariside II DM3DB8X Investigative Icariside II decreases the expression of Bile acid receptor (NR1H4). [36]
TTNPB DMSABD0 Investigative TTNPB increases the activity of Bile acid receptor (NR1H4). [4]
Glycocholic acid DM0SXNM Investigative Glycocholic acid increases the activity of Bile acid receptor (NR1H4). [4]
Glycodeoxycholic acid DM1XEJV Investigative Glycodeoxycholic acid increases the activity of Bile acid receptor (NR1H4). [4]
------------------------------------------------------------------------------------
⏷ Show the Full List of 63 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Dasatinib DMJV2EK Approved Dasatinib decreases the phosphorylation of Bile acid receptor (NR1H4). [16]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Bile acid receptor (NR1H4). [30]
------------------------------------------------------------------------------------
3 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
Eicosapentaenoic acid/docosa-hexaenoic acid DMMUCG4 Approved Eicosapentaenoic acid/docosa-hexaenoic acid affects the binding of Bile acid receptor (NR1H4). [25]
Arachidonic acid DMUOQZD Investigative Arachidonic acid affects the binding of Bile acid receptor (NR1H4). [25]
Alpha-linolenic acid DMY64HE Investigative Alpha-linolenic acid affects the binding of Bile acid receptor (NR1H4). [25]
------------------------------------------------------------------------------------

References

1 Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis. Cell. 2000 Sep 15;102(6):731-44. doi: 10.1016/s0092-8674(00)00062-3.
2 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
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 The farnesoid X receptor FXRalpha/NR1H4 acquired ligand specificity for bile salts late in vertebrate evolution. Am J Physiol Regul Integr Comp Physiol. 2007 Sep;293(3):R1400-9. doi: 10.1152/ajpregu.00781.2006. Epub 2007 Jun 13.
5 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
6 Quantitative high-throughput profiling of environmental chemicals and drugs that modulate farnesoid X receptor. Sci Rep. 2014 Sep 26;4:6437. doi: 10.1038/srep06437.
7 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
8 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
9 Permethrin and ivermectin modulate lipid metabolism in steatosis-induced HepG2 hepatocyte. Food Chem Toxicol. 2019 Mar;125:595-604. doi: 10.1016/j.fct.2019.02.005. Epub 2019 Feb 6.
10 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.
11 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
12 Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach. Toxicology. 2013 Apr 5;306:24-34.
13 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.
14 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
15 Dihydroartemisinin protects against alcoholic liver injury through alleviating hepatocyte steatosis in a farnesoid X receptor-dependent manner. Toxicol Appl Pharmacol. 2017 Jan 15;315:23-34. doi: 10.1016/j.taap.2016.12.001. Epub 2016 Dec 6.
16 Phosphorylation of hepatic farnesoid X receptor by FGF19 signaling-activated Src maintains cholesterol levels and protects from atherosclerosis. J Biol Chem. 2019 May 31;294(22):8732-8744. doi: 10.1074/jbc.RA119.008360. Epub 2019 Apr 17.
17 UDCA and CDCA alleviate 17-ethinylestradiol-induced cholestasis through PKA-AMPK pathways in rats. Toxicol Appl Pharmacol. 2016 Nov 15;311:12-25. doi: 10.1016/j.taap.2016.10.011. Epub 2016 Oct 12.
18 Organochloride pesticides modulated gut microbiota and influenced bile acid metabolism in mice. Environ Pollut. 2017 Jul;226:268-276.
19 Ursodeoxycholic acid but not tauroursodeoxycholic acid inhibits proliferation and differentiation of human subcutaneous adipocytes. PLoS One. 2013 Dec 3;8(12):e82086. doi: 10.1371/journal.pone.0082086. eCollection 2013.
20 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.
21 Transcriptional profiling suggests that Nevirapine and Ritonavir cause drug induced liver injury through distinct mechanisms in primary human hepatocytes. Chem Biol Interact. 2016 Aug 5;255:31-44.
22 Robustness testing and optimization of an adverse outcome pathway on cholestatic liver injury. Arch Toxicol. 2020 Apr;94(4):1151-1172. doi: 10.1007/s00204-020-02691-9. Epub 2020 Mar 10.
23 Omics-based responses induced by bosentan in human hepatoma HepaRG cell cultures. Arch Toxicol. 2018 Jun;92(6):1939-1952.
24 Potency of individual bile acids to regulate bile acid synthesis and transport genes in primary human hepatocyte cultures. Toxicol Sci. 2014 Oct;141(2):538-46. doi: 10.1093/toxsci/kfu151. Epub 2014 Jul 23.
25 Polyunsaturated fatty acids are FXR ligands and differentially regulate expression of FXR targets. DNA Cell Biol. 2004 Aug;23(8):519-26. doi: 10.1089/1044549041562267.
26 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
27 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.
28 Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
29 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.
30 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
31 Retinoid X receptor (RXR) agonist-induced antagonism of farnesoid X receptor (FXR) activity due to absence of coactivator recruitment and decreased DNA binding. J Biol Chem. 2003 Mar 21;278(12):10028-32. doi: 10.1074/jbc.M208312200. Epub 2003 Jan 7.
32 Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
33 Transcriptional Regulation of Human Arylamine N-Acetyltransferase 2 Gene by Glucose and Insulin in Liver Cancer Cell Lines. Toxicol Sci. 2022 Nov 23;190(2):158-172. doi: 10.1093/toxsci/kfac103.
34 Farnesol induces fatty acid oxidation and decreases triglyceride accumulation in steatotic HepaRG cells. Toxicol Appl Pharmacol. 2019 Feb 15;365:61-70.
35 Identification of Yinchenwuling fang's active components and hepatoprotective effects against cholestatic liver damage induced by alpha-naphthyl isothiocyanate in mice. J Chromatogr B Analyt Technol Biomed Life Sci. 2023 Jan 15;1215:123570. doi: 10.1016/j.jchromb.2022.123570. Epub 2022 Dec 8.
36 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.