Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6PK94R)

• DOT Name: Glutathione peroxidase 3 (GPX3)
• Synonyms: GPx-3; GSHPx-3; EC 1.11.1.9; Extracellular glutathione peroxidase; Plasma glutathione peroxidase; GPx-P; GSHPx-P
• Gene Name: GPX3
• Related Disease:
  Acute myelogenous leukaemia
  leukaemia
  Leukemia
  Melanoma
  Myelodysplastic syndrome
  Amyotrophic lateral sclerosis
  Androgen insensitivity syndrome
  Benign neoplasm
  Carcinoma
  Cardiovascular disease
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Endometriosis
  Esophageal squamous cell carcinoma
  Glioblastoma multiforme
  Glycogen storage disease due to GLUT2 deficiency
  Hepatocellular carcinoma
  Liver cancer
  Lung cancer
  Lung neoplasm
  Metastatic malignant neoplasm
  Neoplasm
  Nephropathy
  Non-small-cell lung cancer
  Obesity
  Polycystic ovarian syndrome
  Primary Fanconi syndrome
  Prostate cancer
  Pulmonary disease
  Thyroid tumor
  Gastric cancer
  Stomach cancer
  Adenocarcinoma
  Barrett esophagus
  Coronary atherosclerosis
  Endometrium adenocarcinoma
  Essential hypertension
  Lung carcinoma
  Non-insulin dependent diabetes
  Prostate carcinoma
  Prostate neoplasm
  Stroke
• UniProt ID: GPX3_HUMAN
• PDB ID: 2R37
• EC Number: 1.11.1.9
• Pfam ID: PF00255
• Sequence:
  MARLLQASCLLSLLLAGFVSQSRGQEKSKMDCHGGISGTIYEYGALTIDGEEYIPFKQYA
  GKYVLFVNVASYUGLTGQYIELNALQEELAPFGLVILGFPCNQFGKQEPGENSEILPTLK
  YVRPGGGFVPNFQLFEKGDVNGEKEQKFYTFLKNSCPPTSELLGTSDRLFWEPMKVHDIR
  WNFEKFLVGPDGIPIMRWHHRTTVSNVKMDILSYMRRQAALGVKRK
• Function: Protects cells and enzymes from oxidative damage, by catalyzing the reduction of hydrogen peroxide, lipid peroxides and organic hydroperoxide, by glutathione.
• Tissue Specificity: Secreted in plasma.
• KEGG Pathway:
  Glutathione metabolism (hsa00480)
  Metabolic pathways (hsa01100)
  Thyroid hormone synthesis (hsa04918)
  Amyotrophic lateral sclerosis (hsa05014)
  Huntington disease (hsa05016)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
• Reactome Pathway: Detoxification of Reactive Oxygen Species (R-HSA-3299685)
• BioCyc Pathway: MetaCyc:HS08224-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

43 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Posttranslational Modification	[1]
leukaemia	DISS7D1V	Definitive	Posttranslational Modification	[1]
Leukemia	DISNAKFL	Definitive	Posttranslational Modification	[1]
Melanoma	DIS1RRCY	Definitive	Altered Expression	[2]
Myelodysplastic syndrome	DISYHNUI	Definitive	Posttranslational Modification	[1]
Amyotrophic lateral sclerosis	DISF7HVM	Strong	Genetic Variation	[3]
Androgen insensitivity syndrome	DISUZBBO	Strong	Genetic Variation	[4]
Benign neoplasm	DISDUXAD	Strong	Biomarker	[5]
Carcinoma	DISH9F1N	Strong	Altered Expression	[6]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[7]
Colon cancer	DISVC52G	Strong	Biomarker	[8]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Posttranslational Modification	[9]
Endometriosis	DISX1AG8	Strong	Biomarker	[10]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[11]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[12]
Glycogen storage disease due to GLUT2 deficiency	DISXRSZ1	Strong	Biomarker	[13]
Hepatocellular carcinoma	DIS0J828	Strong	Posttranslational Modification	[14]
Liver cancer	DISDE4BI	Strong	Biomarker	[15]
Lung cancer	DISCM4YA	Strong	Biomarker	[16]
Lung neoplasm	DISVARNB	Strong	Biomarker	[17]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[6]
Neoplasm	DISZKGEW	Strong	Altered Expression	[18]
Nephropathy	DISXWP4P	Strong	Altered Expression	[19]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[20]
Obesity	DIS47Y1K	Strong	Altered Expression	[21]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[22]
Primary Fanconi syndrome	DISR144Y	Strong	Biomarker	[13]
Prostate cancer	DISF190Y	Strong	Biomarker	[23]
Pulmonary disease	DIS6060I	Strong	Biomarker	[24]
Thyroid tumor	DISLVKMD	Strong	Biomarker	[25]
Gastric cancer	DISXGOUK	moderate	Posttranslational Modification	[26]
Stomach cancer	DISKIJSX	moderate	Posttranslational Modification	[26]
Adenocarcinoma	DIS3IHTY	Limited	Genetic Variation	[27]
Barrett esophagus	DIS416Y7	Limited	Biomarker	[28]
Coronary atherosclerosis	DISKNDYU	Limited	Genetic Variation	[29]
Endometrium adenocarcinoma	DISY6744	Limited	Biomarker	[30]
Essential hypertension	DIS7WI98	Limited	Genetic Variation	[31]
Lung carcinoma	DISTR26C	Limited	Biomarker	[16]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[32]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[23]
Prostate neoplasm	DISHDKGQ	Limited	Biomarker	[33]
Stroke	DISX6UHX	Limited	Genetic Variation	[31]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Glutathione peroxidase 3 (GPX3) affects the response to substance of Methotrexate.	[66]
Mitoxantrone	DMM39BF	Approved	Glutathione peroxidase 3 (GPX3) affects the response to substance of Mitoxantrone.	[66]

34 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 Glutathione peroxidase 3 (GPX3).	[34]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Glutathione peroxidase 3 (GPX3).	[35]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Glutathione peroxidase 3 (GPX3).	[36]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Glutathione peroxidase 3 (GPX3).	[37]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Glutathione peroxidase 3 (GPX3).	[38]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Glutathione peroxidase 3 (GPX3).	[39]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Glutathione peroxidase 3 (GPX3).	[40]
Quercetin	DM3NC4M	Approved	Quercetin affects the expression of Glutathione peroxidase 3 (GPX3).	[41]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Glutathione peroxidase 3 (GPX3).	[42]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Glutathione peroxidase 3 (GPX3).	[43]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Glutathione peroxidase 3 (GPX3).	[44]
Selenium	DM25CGV	Approved	Selenium increases the expression of Glutathione peroxidase 3 (GPX3).	[45]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Glutathione peroxidase 3 (GPX3).	[46]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Glutathione peroxidase 3 (GPX3).	[47]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Glutathione peroxidase 3 (GPX3).	[48]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Glutathione peroxidase 3 (GPX3).	[49]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Glutathione peroxidase 3 (GPX3).	[50]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Glutathione peroxidase 3 (GPX3).	[51]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid increases the expression of Glutathione peroxidase 3 (GPX3).	[52]
Ifosfamide	DMCT3I8	Approved	Ifosfamide decreases the activity of Glutathione peroxidase 3 (GPX3).	[13]
Pioglitazone	DMKJ485	Approved	Pioglitazone increases the expression of Glutathione peroxidase 3 (GPX3).	[54]
Sodium phenylbutyrate	DMXLBCQ	Approved	Sodium phenylbutyrate increases the expression of Glutathione peroxidase 3 (GPX3).	[55]
Mercaptopurine	DMTM2IK	Approved	Mercaptopurine increases the expression of Glutathione peroxidase 3 (GPX3).	[50]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol increases the expression of Glutathione peroxidase 3 (GPX3).	[56]
Coprexa	DMA0WEK	Phase 3	Coprexa increases the expression of Glutathione peroxidase 3 (GPX3).	[57]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Glutathione peroxidase 3 (GPX3).	[45]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Glutathione peroxidase 3 (GPX3).	[58]
Disulfiram	DMCL2OK	Phase 2 Trial	Disulfiram increases the expression of Glutathione peroxidase 3 (GPX3).	[58]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Glutathione peroxidase 3 (GPX3).	[60]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Glutathione peroxidase 3 (GPX3).	[61]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of Glutathione peroxidase 3 (GPX3).	[58]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Glutathione peroxidase 3 (GPX3).	[63]
GW7647	DM9RD0C	Investigative	GW7647 increases the expression of Glutathione peroxidase 3 (GPX3).	[64]
THIOCTIC ACID	DMNFCXW	Investigative	THIOCTIC ACID increases the expression of Glutathione peroxidase 3 (GPX3).	[65]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Glutathione peroxidase 3 (GPX3).	[59]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Glutathione peroxidase 3 (GPX3).	[62]

References

• [1] GPX3 methylation in bone marrow predicts adverse prognosis and leukemia transformation in myelodysplastic syndrome.Cancer Med. 2017 Jan;6(1):267-274. doi: 10.1002/cam4.984. Epub 2016 Nov 28.
• [2] Glutathione peroxidase 3 (GPX3) suppresses the growth of melanoma cells through reactive oxygen species (ROS)-dependent stabilization of hypoxia-inducible factor 1- and 2-.J Cell Biochem. 2019 Nov;120(11):19124-19136. doi: 10.1002/jcb.29240. Epub 2019 Jul 16.
• [3] Cross-ethnic meta-analysis identifies association of the GPX3-TNIP1 locus with amyotrophic lateral sclerosis.Nat Commun. 2017 Sep 20;8(1):611. doi: 10.1038/s41467-017-00471-1.
• [4] Plasma glutathione peroxidase in pediatric stroke families.J Thromb Haemost. 2011 Jan;9(1):33-8. doi: 10.1111/j.1538-7836.2010.04103.x.
• [5] GPx3 promoter hypermethylation is a frequent event in human cancer and is associated with tumorigenesis and chemotherapy response.Cancer Lett. 2011 Oct 1;309(1):37-45. doi: 10.1016/j.canlet.2011.05.013.
• [6] Expression and clinical role of chemoresponse-associated genes in ovarian serous carcinoma.Gynecol Oncol. 2015 Oct;139(1):30-9. doi: 10.1016/j.ygyno.2015.07.107. Epub 2015 Jul 29.
• [7] Pre-clinical model of severe glutathione peroxidase-3 deficiency and chronic kidney disease results in coronary artery thrombosis and depressed left ventricular function.Nephrol Dial Transplant. 2018 Jun 1;33(6):923-934. doi: 10.1093/ndt/gfx304.
• [8] Significance of Polymorphisms and Expression of Enzyme-Encoding Genes Related to Glutathione in Hematopoietic Cancers and Solid Tumors.Biomed Res Int. 2015;2015:853573. doi: 10.1155/2015/853573. Epub 2015 Nov 23.
• [9] GPX3 promoter methylation predicts platinum sensitivity in colorectal cancer.Epigenetics. 2017 Jul 3;12(7):540-550. doi: 10.1080/15592294.2016.1265711. Epub 2016 Dec 5.
• [10] Molecular evidence for differences in endometrium in severe versus mild endometriosis.Reprod Sci. 2011 Mar;18(3):229-51. doi: 10.1177/1933719110386241. Epub 2010 Nov 9.
• [11] Promoter methylation and clinical significance of GPX3 in esophageal squamous cell carcinoma.Pathol Res Pract. 2019 Nov;215(11):152676. doi: 10.1016/j.prp.2019.152676. Epub 2019 Sep 27.
• [12] Identification of potential serum biomarkers of glioblastoma: serum osteopontin levels correlate with poor prognosis.Cancer Epidemiol Biomarkers Prev. 2010 Jun;19(6):1409-22. doi: 10.1158/1055-9965.EPI-09-1077.
• [13] Plasma glutathione peroxidase and its relationship to renal proximal tubule function. Mol Genet Metab. 1998 Nov;65(3):238-45. doi: 10.1006/mgme.1998.2760.
• [14] Methylation of promoter and expression silencing of GPX3 gene in hepatocellular carcinoma tissue.Clin Res Hepatol Gastroenterol. 2015 Apr;39(2):198-204. doi: 10.1016/j.clinre.2014.09.003. Epub 2014 Oct 13.
• [15] Evaluation of plasma carcinogenic markers in rat hepatic tumors models induced by rat hepatoma N1-S1 cells and benzo[a]pyrene.Arch Pharm Res. 2010 Feb;33(2):247-55. doi: 10.1007/s12272-010-0210-9. Epub 2010 Feb 24.
• [16] MiR-921 directly downregulates GPx3 in A549 lung cancer cells.Gene. 2019 Jun 5;700:163-167. doi: 10.1016/j.gene.2019.02.086. Epub 2019 Mar 19.
• [17] Varied pathways of stage IA lung adenocarcinomas discovered by integrated gene expression analysis.Int J Biol Sci. 2011 Apr 28;7(5):551-66. doi: 10.7150/ijbs.7.551.
• [18] GPx3 supports ovarian cancer progression by manipulating the extracellular redox environment.Redox Biol. 2019 Jul;25:101051. doi: 10.1016/j.redox.2018.11.009. Epub 2018 Nov 17.
• [19] Sex Differences in Glutathione Peroxidase Activity and Central Obesity in Patients with Type 2 Diabetes at High Risk of Cardio-Renal Disease.Antioxidants (Basel). 2019 Dec 7;8(12):629. doi: 10.3390/antiox8120629.
• [20] Downregulation of microRNA-196a inhibits stem cell self-renewal ability and stemness in non-small-cell lung cancer through upregulating GPX3 expression.Int J Biochem Cell Biol. 2019 Oct;115:105571. doi: 10.1016/j.biocel.2019.105571. Epub 2019 Jul 25.
• [21] Effects of Weight Loss on Glutathione Peroxidase 3 Serum Concentrations and Adipose Tissue Expression in Human Obesity.Obes Facts. 2018;11(6):475-490. doi: 10.1159/000494295. Epub 2018 Dec 11.
• [22] A Low Glycemic Index Decreases Inflammation by Increasing the Concentration of Uric Acid and the Activity of Glutathione Peroxidase (GPx3) in Patients with Polycystic Ovary Syndrome (PCOS).Molecules. 2019 Apr 17;24(8):1508. doi: 10.3390/molecules24081508.
• [23] Troglitazone inhibits the migration and invasion of PC-3 human prostate cancer cells by upregulating E-cadherin and glutathione peroxidase 3.Oncol Lett. 2018 Oct;16(4):5482-5488. doi: 10.3892/ol.2018.9278. Epub 2018 Aug 8.
• [24] NO2-induced acute and chronic lung injury cause imbalance of glutathione metabolism in type II pneumocytes.Med Sci Monit. 2005 Aug;11(8):BR273-9. Epub 2005 Jul 25.
• [25] Silencing GPX3 Expression Promotes Tumor Metastasis in Human Thyroid Cancer.Curr Protein Pept Sci. 2015;16(4):316-21. doi: 10.2174/138920371604150429154840.
• [26] GPX3 hypermethylation in gastric cancer and its prognostic value in patients aged over 60.Future Oncol. 2019 Apr;15(11):1279-1289. doi: 10.2217/fon-2018-0674. Epub 2019 Mar 29.
• [27] Association of Antioxidative Enzymes Polymorphisms with Efficacy of Platin and Fluorouracil-Based Adjuvant Therapy in Gastric Cancer.Cell Physiol Biochem. 2018;48(6):2247-2257. doi: 10.1159/000492642. Epub 2018 Aug 16.
• [28] Overview of major molecular alterations during progression from Barrett's esophagus to esophageal adenocarcinoma.Ann N Y Acad Sci. 2016 Oct;1381(1):74-91. doi: 10.1111/nyas.13134. Epub 2016 Jul 14.
• [29] MnSOD, CAT and GPx-3 genetic polymorphisms in coronary artery disease.Mol Biol Rep. 2019 Feb;46(1):841-845. doi: 10.1007/s11033-018-4539-3. Epub 2019 Jan 2.
• [30] Gene expression profiling predicts a three-gene expression signature of endometrial adenocarcinoma in a rat model.Cancer Cell Int. 2009 May 8;9:12. doi: 10.1186/1475-2867-9-12.
• [31] The C718T polymorphism in the 3'-untranslated region of glutathione peroxidase-4 gene is a predictor of cerebral stroke in patients with essential hypertension.Hypertens Res. 2012 May;35(5):507-12. doi: 10.1038/hr.2011.213. Epub 2011 Dec 8.
• [32] Selenium Levels in Community Dwellers with Type 2 Diabetes Mellitus.Biol Trace Elem Res. 2019 Oct;191(2):354-362. doi: 10.1007/s12011-019-1645-6. Epub 2019 Feb 6.
• [33] Glutathione peroxidase 3, deleted or methylated in prostate cancer, suppresses prostate cancer growth and metastasis.Cancer Res. 2007 Sep 1;67(17):8043-50. doi: 10.1158/0008-5472.CAN-07-0648.
• [34] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [35] 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.
• [36] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [37] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [38] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [39] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [40] Gene expression profiling of human peri-implantation endometria between natural and stimulated cycles. Fertil Steril. 2008 Dec;90(6):2152-64.
• [41] 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.
• [42] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [43] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [44] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [45] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [46] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [47] Dexamethasone and the inflammatory response in explants of human omental adipose tissue. Mol Cell Endocrinol. 2010 Feb 5;315(1-2):292-8.
• [48] Cannabidiol induces antioxidant pathways in keratinocytes by targeting BACH1. Redox Biol. 2020 Jan;28:101321. doi: 10.1016/j.redox.2019.101321. Epub 2019 Sep 5.
• [49] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [50] Petit E, Langouet S, Akhdar H, Nicolas-Nicolaz C, Guillouzo A, Morel F. Differential toxic effects of azathioprine, 6-mercaptopurine and 6-thioguanine on human hepatocytes. Toxicol In Vitro. 2008;22(3):632-642. [PMID: 18222062]
• [51] In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells. Mol Cancer Ther. 2005 Jun;4(6):885-900.
• [52] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [53] Plasma glutathione peroxidase and its relationship to renal proximal tubule function. Mol Genet Metab. 1998 Nov;65(3):238-45. doi: 10.1006/mgme.1998.2760.
• [54] Peroxisome proliferator activated receptor gamma (PPAR-gama) ligand pioglitazone regulated gene networks in term human primary trophoblast cells. Reprod Toxicol. 2018 Oct;81:99-107.
• [55] Gene expression profile analysis of 4-phenylbutyrate treatment of IB3-1 bronchial epithelial cell line demonstrates a major influence on heat-shock proteins. Physiol Genomics. 2004 Jan 15;16(2):204-11.
• [56] Expression profiling in squamous carcinoma cells reveals pleiotropic effects of vitamin D3 analog EB1089 signaling on cell proliferation, differentiation, and immune system regulation. Mol Endocrinol. 2002 Jun;16(6):1243-56.
• [57] Copper chelator ATN-224 inhibits endothelial function by multiple mechanisms. Microvasc Res. 2009 May;77(3):314-26.
• [58] Keratinocyte gene expression profiles discriminate sensitizing and irritating compounds. Toxicol Sci. 2010 Sep;117(1):81-9.
• [59] 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.
• [60] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [61] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [62] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [63] In vitro gene expression data supporting a DNA non-reactive genotoxic mechanism for ochratoxin A. Toxicol Appl Pharmacol. 2007 Apr 15;220(2):216-24.
• [64] Identifying qualitative differences in PPAR signaling networks in human and rat hepatocytes and their significance for next generation chemical risk assessment methods. Toxicol In Vitro. 2020 Apr;64:104463. doi: 10.1016/j.tiv.2019.02.017. Epub 2019 Oct 15.
• [65] Cytoprotective effect of alpha-lipoic acid on paraquat-exposed human bronchial epithelial cells via activation of nuclear factor erythroid related factor-2 pathway. Biol Pharm Bull. 2013;36(5):802-11.
• [66] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.