Details of Xenobiotics-DME Interaction (XEOTIC)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0014)
DME Name Thiopurine methyltransferase (TPMT), Homo sapiens DME Info
UniProt ID
TPMT_HUMAN
EC Number    EC: 2.1.1.67     (Click to Show/Hide the Complete EC Tree)
Transferase
Methylase
Methyltransferase
EC: 2.1.1.67
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)
                  Pesticide/Insecticide Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              Dicrotophos Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01050   XEOTIC Info Gene Form mRNA
                                 Classification Pesticide/Insecticide
                                 DME Modulation Dicrotophos inhibits the expression of DME TPMT [1]
                              Parathion Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01064   XEOTIC Info Gene Form Protein
                                 Classification Pesticide/Insecticide
                                 DME Modulation Parathion induces the drug-metabolizing activity of DME TPMT [2]
      Natural Product(s), Extract(s) or Medicine(s)
                  Natural Product Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Senecionine Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01585   XEOTIC Info Gene Form Protein
                                 Classification Natural Product
                                 DME Modulation Senecionine induces the drug-metabolizing activity of DME TPMT [3], [4]
      Pharmaceutical Agent(s)
                  Approved/Marketed Drug Click to Show/Hide the Full List of Xenobiotics:        9 Xenobiotics
                              Bendroflumethiazide Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00234   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Bendrof DMElumethiazide inhibits the drug-metabolizing activity of DME TPMT [5]
                              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 TPMT [6]
                              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 TPMT [7], [8]
                              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 TPMT [9]
                              Furosemide Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00040   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Furosemide inhibits the drug-metabolizing activity of DME TPMT [5]
                              Irinotecan hydrochloride Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00301   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Irinotecan hydrochloride up-regulates the expression of DME TPMT [10]
                              Theophylline Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00005   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Theophylline up-regulates the expression of DME TPMT [11]
                              Trichlormethiazide Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00221   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Trichlormethiazide inhibits the expression of DME TPMT [12]
                              Vorinostat Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00079   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Vorinostat induces the drug-metabolizing activity of DME TPMT [13]
References
1 Molecular mechanisms of discrotophos-induced toxicity in HepG2 cells: The role of CSA in oxidative stress. Food Chem Toxicol. 2017 May;103:253-260.
2 A benzimidazole fungicide, benomyl, and its metabolite, carbendazim, induce aromatase activity in a human ovarian granulose-like tumor cell line (KGN). Endocrinology. 2004 Apr;145(4):1860-9.
3 Role for the PI3K/Akt/Nrf2 signaling pathway in the protective effects of carnosic acid against methylglyoxal-induced neurotoxicity in SH-SY5Y neuroblastoma cells. Chem Biol Interact. 2015 Dec 5;242:396-406.
4 Protective effect of carnosic acid against paraquat-induced redox impairment and mitochondrial dysfunction in SH-SY5Y cells: Role for PI3K/Akt/Nrf2 pathway. Toxicol In Vitro. 2016 Apr;32:41-54.
5 Inhibition of human thiopurine methyltransferase by furosemide, bendroflumethiazide and trichlormethiazide. Eur J Clin Pharmacol. 1996;49(5):393-6.
6 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
7 Cyclosporine A treated in vitro models induce cholestasis response through comparison of phenotype-directed gene expression analysis of in vivo Cyclosporine A-induced cholestasis. Toxicol Lett. 2013 Aug 29;221(3):225-36.
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 Human drug metabolism genes in parathion-and estrogen-treated breast cells. Int J Mol Med. 2007 Dec;20(6):875-81.
10 Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
11 The transcriptional signature of dioxin in human hepatoma HepG2 cells. Biochem Pharmacol. 2000 Oct 15;60(8):1129-42.
12 Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights CYP26 cytochrome metabolism in differential all-trans retinoic acid sensitivity. Blood. 2007 May 15;109(10):4450-60.
13 Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.

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