Details of Xenobiotics-DME Interaction (XEOTIC)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0389)
DME Name Bifunctional epoxide hydrolase 2 (EPHX2), Homo sapiens DME Info
UniProt ID
HYES_HUMAN
EC Number    EC: 3.3.2.10     (Click to Show/Hide the Complete EC Tree)
Hydrolases
Ether hydrolase
Ether hydrolase
EC: 3.3.2.10
Lineage    Species: Homo sapiens     (Click to Show/Hide the Complete Species Lineage)
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Interactome
Interactions between Xenobiotics and DME (XEOTIC)
      Health or Environmental Toxicant(s)
                  Biotoxin Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Dinophysistoxin 1 Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00813   XEOTIC Info Gene Form mRNA
                                 Classification Biotoxin
                                 DME Modulation Dinophysistoxin 1 inhibits the expression of DME EPHX2 [1]
                  Carcinogen Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              Benzo(a)pyrene Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00898   XEOTIC Info Gene Form mRNA
                                 Classification Carcinogen
                                 DME Modulation Benzo(a)pyrene inhibits the expression of DME EPHX2 [2]
                              Aflatoxin B1 Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00806   XEOTIC Info Gene Form mRNA
                                 Classification Carcinogen-mycotoxin
                                 DME Modulation Aflatoxin B1 inhibits the expression of DME EPHX2 [3], [4]
                  Health Hazard/Toxicant Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Diethylhexyl phthalate Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01004   XEOTIC Info Gene Form mRNA
                                 Classification Health Hazard
                                 DME Modulation Diethylhexyl phthalate inhibits the expression of DME EPHX2 [5]
      Natural Product(s), Extract(s) or Medicine(s)
                  Natural Product Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              Heliotrine Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01551   XEOTIC Info Gene Form mRNA
                                 Classification Natural Product
                                 DME Modulation Heliotrine inhibits the expression of DME EPHX2 [6]
                              Senecionine Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01585   XEOTIC Info Gene Form Protein
                                 Classification Natural Product
                                 DME Modulation Senecionine inhibits the drug-metabolizing activity of DME EPHX2 [7]
                  Traditional Medicine Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Jinfukang Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00760   XEOTIC Info Gene Form mRNA
                                 Classification Traditional Medicine
                                 DME Modulation Jinfukang up-regulates the expression of DME EPHX2 [8]
      Pharmaceutical Agent(s)
                  Approved/Marketed Drug Click to Show/Hide the Full List of Xenobiotics:      13 Xenobiotics
                              Acetaminophen Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00217   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Acetaminophen inhibits the expression of DME EPHX2 [9]
                              Arsenic trioxide Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00339   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Arsenic trioxide up-regulates the expression of DME EPHX2 [10]
                              Cisplatin Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00334   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Cisplatin up-regulates the expression of DME EPHX2 [8]
                              Copper sulfate Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00117   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Copper sulfate inhibits the expression of DME EPHX2 [11]
                              Cyclosporine Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00241   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Cyclosporine inhibits the expression of DME EPHX2 [12]
                              Doxorubicin hydrochloride Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00292   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Doxorubicin hydrochloride inhibits the expression of DME EPHX2 [13]
                              Leflunomide Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00053   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Leflunomide inhibits the expression of DME EPHX2 [14]
                              Phenobarbital Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00410   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Phenobarbital inhibits the drug-metabolizing activity of DME EPHX2 [15]
                              Pyrithione zinc Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00399   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Pyrithione zinc up-regulates the expression of DME EPHX2 [16]
                              Troglitazone Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00086   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Troglitazone up-regulates the expression of DME EPHX2 [17]
                              Urethane Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00435   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Urethane inhibits the drug-metabolizing activity of DME EPHX2 [18]
                              Valproic acid Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00029   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Valproic acid inhibits the expression of DME EPHX2 [19], [20]
                              Chlorobenzene Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00442   XEOTIC Info Gene Form mRNA
                                 Classification Drug Marketed but not Approved by US FDA
                                 DME Modulation Chlorobenzene inhibits the expression of DME EPHX2 [21]
                  Drug in Phase 3 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Resveratrol Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00568   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 3
                                 DME Modulation Resveratrol up-regulates the expression of DME EPHX2 [22]
                  Drug in Phase 2 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        3 Xenobiotics
                              AR-9281 Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01083   XEOTIC Info Gene Form Protein
                                 Classification Highest Clinical Status: Phase 2
                                 DME Modulation AR-9281 inhibits the drug-metabolizing activity of DME EPHX2 [23]
                              Ebselen Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00544   XEOTIC Info Gene Form Protein
                                 Classification Highest Clinical Status: Phase 2
                                 DME Modulation Ebselen inhibits the drug-metabolizing activity of DME EPHX2 (IC50 = 2.2 microM) [24]
                              Genistein Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00557   XEOTIC Info Gene Form Protein
                                 Classification Highest Clinical Status: Phase 2
                                 DME Modulation Genistein induces the drug-metabolizing activity of DME EPHX2 [25]
                  Drug in Phase 1 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              NSC 703786 Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01107   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 1
                                 DME Modulation NSC 703786 inhibits the expression of DME EPHX2 [26]
                  Preclinical/Patented Drug Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              K-7174 Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01348   XEOTIC Info Gene Form mRNA
                                 Classification Patented Pharmaceutical Agent
                                 DME Modulation K-7174 inhibits the expression of DME EPHX2 [27]
                  Investigative Agent Click to Show/Hide the Full List of Xenobiotics:        4 Xenobiotics
                              5-Hydroxyeicosatetraenoic acid Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01160   XEOTIC Info Gene Form Protein
                                 Classification Investigative Agent
                                 DME Modulation 5-Hydroxyeicosatetraenoic acid induces the drug-metabolizing activity of DME EPHX2 [28]
                              Indirubin-3'-monoxime Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01342   XEOTIC Info Gene Form mRNA
                                 Classification Investigative Agent
                                 DME Modulation Indirubin-3'-monoxime inhibits the expression of DME EPHX2 [29]
                              Metribolone Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01378   XEOTIC Info Gene Form mRNA
                                 Classification Investigative Agent
                                 DME Modulation Metribolone up-regulates the expression of DME EPHX2 [30]
                              Phenylmercuric acetate Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00818   XEOTIC Info Gene Form mRNA
                                 Classification Investigative Agent
                                 DME Modulation Phenylmercuric acetate inhibits the expression of DME EPHX2 [31]
References
1 Whole genome mRNA transcriptomics analysis reveals different modes of action of the diarrheic shellfish poisons okadaic acid and dinophysis toxin-1 versus azaspiracid-1 in Caco-2 cells. Toxicol In Vitro. 2018 Feb;46:102-112.
2 New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
3 Identification of early target genes of aflatoxin B1 in human hepatocytes, inter-individual variability and comparison with other genotoxic compounds. Toxicol Appl Pharmacol. 2012 Jan 15;258(2):176-87.
4 Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma. Toxicology. 2016 Mar 28;350-352:31-9.
5 Di-(2-ethylhexyl)-phthalate induces apoptosis via the PPARgama/PTEN/AKT pathway in differentiated human embryonic stem cells. Food Chem Toxicol. 2019 Sep;131:110552.
6 Disturbance of gene expression in primary human hepatocytes by hepatotoxic pyrrolizidine alkaloids: A whole genome transcriptome analysis. Toxicol In Vitro. 2015 Oct;29(7):1669-82.
7 Selective inhibition of cytochrome P450 2D6 by Sarpogrelate and its active metabolite, M-1, in human liver microsomes. Drug Metab Dispos. 2014 Jan;42(1):33-9.
8 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
9 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
10 Arsenic trioxide induces different gene expression profiles of genes related to growth and apoptosis in glioma cells dependent on the p53 status. Mol Biol Rep. 2008 Sep;35(3):421-9.
11 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
12 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
13 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.
14 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
15 Reverse type I binding spectra of human cytochrome P450 1B1 induced by flavonoid, stilbene, pyrene, naphthalene, phenanthrene, and biphenyl derivatives that inhibit catalytic activity: a structure-function relationship study. Chem Res Toxicol. 2009 Jul;22(7):1325-33.
16 Integrated analysis of microRNA and mRNA expression profiles highlights aldehyde-induced inflammatory responses in cells relevant for lung toxicity. Toxicology. 2015 Aug 6;334:111-21.
17 Organophosphorus flame retardants impair intracellular lipid metabolic function in human hepatocellular cells. Chem Res Toxicol. 2019 Jun 17;32(6):1250-1258.
18 In vitro inhibition of human small intestinal and liver microsomal astemizole O-demethylation: different contribution of CYP2J2 in the small intestine and liver. Xenobiotica. 2003 Jun;33(6):615-23.
19 Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
20 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.
21 Chlorobenzene induces oxidative stress in human lung epithelial cells in vitro. Toxicol Appl Pharmacol. 2010 Jan 1;242(1):100-8.
22 The THP-1 cell toolbox: a new concept integrating the key events of skin sensitization. Arch Toxicol. 2019 Apr;93(4):941-951.
23 Soluble epoxide hydrolase inhibitor, APAU, protects dopaminergic neurons against rotenone induced neurotoxicity: Implications for Parkinson's disease. Neurotoxicology. 2019 Jan;70:135-145.
24 Inhibition of soluble epoxide hydrolase by fulvestrant and sulfoxides. Bioorg Med Chem Lett. 2013 Jul 1;23(13):3818-21.
25 Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
26 Aryl hydrocarbon receptor ligand 5F 203 induces oxidative stress that triggers DNA damage in human breast cancer cells. Chem Res Toxicol. 2015 May 18;28(5):855-71.
27 A low-molecular-weight compound K7174 represses hepcidin: possible therapeutic strategy against anemia of chronic disease. PLoS One. 2013 Sep 27;8(9):e75568.
28 5-, 12- and 15-Hydroxyeicosatetraenoic acids induce cellular hypertrophy in the human ventricular cardiomyocyte, RL-14 cell line, through MAPK- and NF-B-dependent mechanism. Arch Toxicol. 2016 Feb;90(2):359-73.
29 The effects of indirubin-3'-monoxime, a novel AHR ligand, on stress and toxicity-related gene/protein expression in human U937 cells undergoing differentiation and activation. J Immunotoxicol. 2006 Jan 1;3(1):1-10.
30 Microarray data mining for potential selenium targets in chemoprevention of prostate cancer. Cancer Genomics Proteomics. 2005 Apr;2(2):97-114.
31 Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.

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