Details of Xenobiotics-DME Interaction (XEOTIC)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0048)
DME Name UDP-glucuronosyltransferase 1A4 (UGT1A4), Homo sapiens DME Info
UniProt ID
UD14_HUMAN
EC Number    EC: 2.4.1.17     (Click to Show/Hide the Complete EC Tree)
Transferase
Glycosyltransferases
Hexosyltransferase
EC: 2.4.1.17
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)
                  Acute Toxic Substance Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Usnic acid Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01497   XEOTIC Info Gene Form mRNA
                                 Classification Acute Toxic Substance
                                 DME Modulation Usnic acid up-regulates the expression of DME UGT1A4 [1]
                  Carcinogen Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              Benzo(a)pyrene Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00898   XEOTIC Info Gene Form Protein
                                 Classification Carcinogen
                                 DME Modulation Benzo(a)pyrene induces the drug-metabolizing activity of DME UGT1A4 [2]
                              Methylcholanthrene Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00899   XEOTIC Info Gene Form mRNA
                                 Classification Carcinogen
                                 DME Modulation Methylcholanthrene up-regulates the expression of DME UGT1A4 [3]
                  Health Hazard/Toxicant Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Pirinixic acid Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01433   XEOTIC Info Gene Form Protein
                                 Classification Health Hazard
                                 DME Modulation Pirinixic acid up-regulates the expression of DME UGT1A4 and leads to increasing the drug-metabolizing activity of this enzyme [4]
      Natural Product(s), Extract(s) or Medicine(s)
                  Natural Mixture Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Amphibole asbestos Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00995   XEOTIC Info Gene Form Protein
                                 Classification Natural Mixture
                                 DME Modulation Amphibole asbestos inhibits the drug-metabolizing activity of DME UGT1A4 [5]
                  Natural Product Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Amentoflavone Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01195   XEOTIC Info Gene Form Protein
                                 Classification Natural Product
                                 DME Modulation Amentof DMElavone inhibits the drug-metabolizing activity of DME UGT1A4 [6]
      Pharmaceutical Agent(s)
                  Approved/Marketed Drug Click to Show/Hide the Full List of Xenobiotics:        4 Xenobiotics
                              Obeticholic acid Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00165   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Obeticholic acid inhibits the drug-metabolizing activity of DME UGT1A4 [7]
                              Omeprazole Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00069   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Omeprazole up-regulates the expression of DME UGT1A4 [8], [9]
                              Phenobarbital Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00410   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Phenobarbital up-regulates the expression of DME UGT1A4 [10]
                              Trifluoperazine Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00386   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Trifluoperazine up-regulates the expression of DME UGT1A4 [11]
                  Drug in Phase 2 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              Butyric acid Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01230   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 2/3
                                 DME Modulation Butyric acid up-regulates the expression of DME UGT1A4 [12]
                              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 UGT1A4 [13]
                  Preclinical/Patented Drug Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              (+)-JQ1 Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00723   XEOTIC Info Gene Form mRNA
                                 Classification Drug in Preclinical Study
                                 DME Modulation (+)-JQ1 inhibits the expression of DME UGT1A4 [14]
                  Investigative Agent Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Beta-naphthoflavone Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01220   XEOTIC Info Gene Form mRNA
                                 Classification Investigative Agent
                                 DME Modulation Beta-naphthoflavone up-regulates the expression of DME UGT1A4 [15]
References
1 Increased sensitivity for troglitazone-induced cytotoxicity using a human in vitro co-culture model. Toxicol In Vitro. 2009 Oct;23(7):1387-95.
2 Human CYP1A1GFP expression in transgenic mice serves as a biomarker for environmental toxicant exposure. Toxicol Sci. 2007 Jan;95(1):98-107.
3 Keratinocyte gene expression profiles discriminate sensitizing and irritating compounds. Toxicol Sci. 2010 Sep;117(1):81-9.
4 Glucocorticoid receptor enhancement of pregnane X receptor-mediated CYP2B6 regulation in primary human hepatocytes. Drug Metab Dispos. 2003 May;31(5):620-30.
5 Effect of size fractionation on the toxicity of amosite and Libby amphibole asbestos. Toxicol Sci. 2010 Dec;118(2):420-34.
6 Amentoflavone is a potent broad-spectrum inhibitor of human UDP-glucuronosyltransferases. Chem Biol Interact. 2018 Mar 25;284:48-55.
7 Inhibition potential of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolites on the in vitro monoamine oxidase (MAO)-catalyzed deamination of the neurotransmitters serotonin and dopamine. Toxicol Lett. 2016 Jan 22;243:48-55.
8 Toxicogenomics-based identification of mechanisms for direct immunotoxicity. Toxicol Sci. 2013 Oct;135(2):328-46.
9 Transcriptome-based functional classifiers for direct immunotoxicity. Arch Toxicol. 2014 Mar;88(3):673-89.
10 Pyrethroids: cytotoxicity and induction of CYP isoforms in human hepatocytes. Drug Metabol Drug Interact. 2008;23(3-4):211-36.
11 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
12 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.
13 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.
14 CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
15 Use of mRNA expression to detect the induction of drug metabolising enzymes in rat and human hepatocytes. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):86-96.

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