Details of Xenobiotics-DME Interaction (XEOTIC)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0043)
DME Name Catechol O-methyltransferase (COMT), Homo sapiens DME Info
UniProt ID
COMT_HUMAN
EC Number    EC: 2.1.1.6     (Click to Show/Hide the Complete EC Tree)
Transferase
Methylase
Methyltransferase
EC: 2.1.1.6
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)
      Fungicide(s), Herbicide(s) or Insecticide(s)
                  Fungicide Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Hexachlorobenzene Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00951   XEOTIC Info Gene Form Protein
                                 Classification Fungicide
                                 DME Modulation Hexachlorobenzene induces the drug-metabolizing activity of DME COMT [1]
      Health or Environmental Toxicant(s)
                  Acute Toxic Substance Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Okadaic acid Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01409   XEOTIC Info Gene Form mRNA
                                 Classification Acute Toxic Substance
                                 DME Modulation Okadaic acid inhibits the expression of DME COMT [2]
                  Health Hazard/Toxicant Click to Show/Hide the Full List of Xenobiotics:        3 Xenobiotics
                              Butylbenzyl phthalate Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00998   XEOTIC Info Gene Form mRNA
                                 Classification Health and Environmental Toxicant
                                 DME Modulation Butylbenzyl phthalate inhibits the expression of DME COMT [3]
                              Dibutyl phthalate Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01275   XEOTIC Info Gene Form mRNA
                                 Classification Health and Environmental Toxicant
                                 DME Modulation Dibutyl phthalate inhibits the expression of DME COMT [3]
                              Diethylhexyl phthalate Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01004   XEOTIC Info Gene Form mRNA
                                 Classification Health Hazard
                                 DME Modulation Diethylhexyl phthalate up-regulates the expression of DME COMT [4]
      Natural Product(s), Extract(s) or Medicine(s)
                  Natural Mixture Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Dust Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01284   XEOTIC Info Gene Form mRNA
                                 Classification Natural Mixture
                                 DME Modulation Dust inhibits the expression of DME COMT [5]
                  Natural Product Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Oleacein Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01410   XEOTIC Info Gene Form mRNA
                                 Classification Natural Product
                                 DME Modulation Oleacein inhibits the expression of DME COMT [2]
      Pharmaceutical Agent(s)
                  Approved/Marketed Drug Click to Show/Hide the Full List of Xenobiotics:      10 Xenobiotics
                              Aminoglutethimide Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00233   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Aminoglutethimide induces the drug-metabolizing activity of DME COMT [6]
                              Entacapone Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00185   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Entacapone inhibits the drug-metabolizing activity of DME COMT (IC50 = 0.386 microM) [7]
                              Estradiol Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00090   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Estradiol inhibits the drug-metabolizing activity of DME COMT [8], [9]
                              Hydrogen peroxide Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00388   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Hydrogen peroxide inhibits the expression of DME COMT [10]
                              Megestrol acetate Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00109   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Megestrol acetate up-regulates the expression of DME COMT [11]
                              Progesterone Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00094   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Progesterone inhibits the expression of DME COMT [12]
                              Tolcapone Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00182   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Tolcapone inhibits the drug-metabolizing activity of DME COMT (IC50 = 0.127 microM) [7]
                              Tretinoin Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00253   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Tretinoin up-regulates the expression of DME COMT [13], [14]
                              Valproic acid Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00029   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Valproic acid inhibits the drug-metabolizing activity of DME COMT [15]
                              Daidzein Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00439   XEOTIC Info Gene Form Protein
                                 Classification Drug Marketed but not Approved by US FDA
                                 DME Modulation Daidzein inhibits the drug-metabolizing activity of DME COMT [8], [9]
                  Drug in Phase 2 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        3 Xenobiotics
                              Butyric acid Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01230   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 2/3
                                 DME Modulation Butyric acid inhibits the expression of DME COMT [16]
                              Bisphenol A Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01226   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 2
                                 DME Modulation Bisphenol A inhibits the expression of DME COMT [17], [3]
                              Genistein Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00557   XEOTIC Info Gene Form Protein
                                 Classification Highest Clinical Status: Phase 2
                                 DME Modulation Genistein inhibits the drug-metabolizing activity of DME COMT [8], [9]
                  Drug in Phase 1 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Fingolimod hydrochloride Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00554   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 1
                                 DME Modulation Fingolimod hydrochloride up-regulates the expression of DME COMT [18]
                  Preclinical/Patented Drug Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              ICG-001 Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01336   XEOTIC Info Gene Form mRNA
                                 Classification Patented Pharmaceutical Agent
                                 DME Modulation ICG-001 up-regulates the expression of DME COMT [19]
                              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 COMT [20]
                  Investigative Agent Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              4-hydroxy-2-nonenal Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00869   XEOTIC Info Gene Form mRNA
                                 Classification Investigative Agent
                                 DME Modulation 4-hydroxy-2-nonenal inhibits the expression of DME COMT [10]
                              Coumestrol Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01261   XEOTIC Info Gene Form mRNA
                                 Classification Investigative Agent
                                 DME Modulation Coumestrol inhibits the expression of DME COMT [21]
References
1 Hexachlorobenzene and pentachlorobenzene accumulation, metabolism and effect on steroid secretion and on CYP11A1 and CYP19 expression in cultured human placental tissue. Reprod Toxicol. 2014 Jan;43:102-10.
2 Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
3 Assessment of cellular estrogenic activity based on estrogen receptor-mediated reduction of soluble-form catechol-O-methyltransferase (COMT) expression in an ELISA-based system. PLoS One. 2013 Sep 6;8(9):e74065.
4 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.
5 Differential response of Mono Mac 6, BEAS-2B, and Jurkat cells to indoor dust. Environ Health Perspect. 2007 Sep;115(9):1325-32.
6 Proteomic profile of aminoglutethimide-induced apoptosis in HL-60 cells: role of myeloperoxidase and arylamine free radicals. Chem Biol Interact. 2015 Sep 5;239:129-38.
7 Identification of potential off-target toxicity liabilities of catechol-O-methyltransferase inhibitors by differential competition capture compound mass spectrometry. J Med Chem. 2016 May 26;59(10):4664-75.
8 Soy isoflavones decrease the catechol-O-methyltransferase-mediated inactivation of 4-hydroxyestradiol in cultured MCF-7 cells. Carcinogenesis. 2008 Feb;29(2):363-70.
9 Phytoestrogens modulate the expression of 17alpha-estradiol metabolizing enzymes in cultured MCF-7 cells. Adv Exp Med Biol. 2008;617:625-32.
10 Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
11 Benzodiazepines medazepam and midazolam are activators of pregnane X receptor and weak inducers of CYP3A4: investigation in primary cultures of human hepatocytes and hepatocarcinoma cell lines. Toxicol Lett. 2010 Mar 15;193(2):183-8.
12 Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway. Sci Rep. 2019 Jan 24;9(1):675.
13 Comparison of cellular and transcriptomic effects between electronic cigarette vapor and cigarette smoke in human bronchial epithelial cells. Toxicol In Vitro. 2017 Dec;45(Pt 3):417-425.
14 Inflammatory transcriptome profiling of human monocytes exposed acutely to cigarette smoke. PLoS One. 2012;7(2):e30120.
15 Carbonic anhydrase inhibitorsInhibition of isozymes I, II, IV, V, and IX with anions isosteric and isoelectronic with sulfate, nitrate, and carbonate. Bioorg Med Chem Lett. 2005 Feb 1;15(3):567-71.
16 Butyrate interacts with benzo[a]pyrene to alter expression and activities of xenobiotic metabolizing enzymes involved in metabolism of carcinogens within colon epithelial cell models. Toxicology. 2019 Jan 15;412:1-11.
17 Bisphenol A-associated alterations in the expression and epigenetic regulation of genes encoding xenobiotic metabolizing enzymes in human fetal liver. Environ Mol Mutagen. 2014 Apr;55(3):184-95.
18 Fingolimod interrupts the cross talk between estrogen metabolism and sphingolipid metabolism within prostate cancer cells. Toxicol Lett. 2018 Jul;291:77-85.
19 Altering cancer transcriptomes using epigenomic inhibitors. Epigenetics Chromatin. 2015 Feb 24;8:9.
20 A low-molecular-weight compound K7174 represses hepcidin: possible therapeutic strategy against anemia of chronic disease. PLoS One. 2013 Sep 27;8(9):e75568.
21 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.

If you find any error in data or bug in web service, please kindly report it to Dr. Yin and Dr. Li.