Details of Xenobiotics-DME Interaction (XEOTIC)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0051)
DME Name N-acetyltransferase 2 (NAT2), Homo sapiens DME Info
UniProt ID
ARY2_HUMAN
EC Number    EC: 2.3.1.5     (Click to Show/Hide the Complete EC Tree)
Transferase
Acyltransferase
Acyltransferase
EC: 2.3.1.5
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:        2 Xenobiotics
                              2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01119   XEOTIC Info Gene Form mRNA
                                 Classification Acute Toxic Substance
                                 DME Modulation 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine inhibits the expression of DME NAT2 [1]
                              Iodoacetamide Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01346   XEOTIC Info Gene Form Protein
                                 Classification Acute Toxic Substance
                                 DME Modulation Iodoacetamide inhibits the drug-metabolizing activity of DME NAT2 [2]
                  Carcinogen Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              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 NAT2 [3]
      Pharmaceutical Agent(s)
                  Approved/Marketed Drug Click to Show/Hide the Full List of Xenobiotics:        8 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 NAT2 [4], [5]
                              Calcitriol Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00184   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Calcitriol inhibits the expression of DME NAT2 [6]
                              Carbamazepine Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00011   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Carbamazepine up-regulates the expression of DME NAT2 [7]
                              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 NAT2 [8], [9]
                              Estradiol Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00090   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Estradiol inhibits the expression of DME NAT2 [8]
                              Hydrogen peroxide Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00388   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Hydrogen peroxide inhibits the drug-metabolizing activity of DME NAT2 [10]
                              Testosterone Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00095   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Testosterone up-regulates the expression of DME NAT2 [11]
                              Valproic acid Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00029   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Valproic acid up-regulates the expression of DME NAT2 [12]
                  Drug in Phase 2 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        1 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 NAT2 [13]
                  Drug in Phase 1 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Trichostatin A Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01492   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 1
                                 DME Modulation Trichostatin A up-regulates the expression of DME NAT2 [14]
References
1 Protective effects of xanthohumol against the genotoxicity of heterocyclic aromatic amines MeIQx and PhIP in bacteria and in human hepatoma (HepG2) cells. Food Chem Toxicol. 2012 Mar;50(3-4):949-55.
2 Cyanamide-mediated inhibition of N-acetyltransferase 1. Toxicology. 2012 Dec 8;302(1):1-10.
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 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.
5 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
6 Vitamin D3 transactivates the zinc and manganese transporter SLC30A10 via the Vitamin D receptor. J Steroid Biochem Mol Biol. 2016 Oct;163:77-87.
7 Transcriptional profiling of genes induced in the livers of patients treated with carbamazepine. Clin Pharmacol Ther. 2006 Nov;80(5):440-456.
8 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.
9 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
10 The xenobiotic-metabolizing enzymes arylamine N-acetyltransferases in human lens epithelial cells: inactivation by cellular oxidants and UVB-induced oxidative stress. Mol Pharmacol. 2005 Apr;67(4):1299-306.
11 Structure-dependent modulation of aryl hydrocarbon receptor-mediated activities by flavonoids. Toxicol Sci. 2018 Jul 1;164(1):205-217.
12 Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
13 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.
14 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.

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