Details of Xenobiotics-DME Interaction (XEOTIC)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0096)
DME Name Myeloperoxidase (MPO), Homo sapiens DME Info
UniProt ID
PERM_HUMAN
EC Number    EC: 1.11.2.2     (Click to Show/Hide the Complete EC Tree)
Oxidoreductase
Peroxidase
Peroxygenase
EC: 1.11.2.2
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)
                  Health Hazard/Toxicant Click to Show/Hide the Full List of Xenobiotics:        4 Xenobiotics
                              1-methyl-4-phenylpyridinium Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01103   XEOTIC Info Gene Form mRNA
                                 Classification Health Hazard
                                 DME Modulation 1-methyl-4-phenylpyridinium up-regulates the expression of DME MPO [1]
                              Caffeic acid Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01232   XEOTIC Info Gene Form Protein
                                 Classification Health Hazard
                                 DME Modulation Caffeic acid inhibits the drug-metabolizing activity of DME MPO [2]
                              Dimethyl formamide Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01279   XEOTIC Info Gene Form mRNA
                                 Classification Health Hazard
                                 DME Modulation Dimethyl formamide up-regulates the expression of DME MPO [3]
                              Hirudin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01330   XEOTIC Info Gene Form Protein
                                 Classification Health Hazard
                                 DME Modulation Hirudin inhibits the drug-metabolizing activity of DME MPO [4]
      Natural Product(s), Extract(s) or Medicine(s)
                  Natural Mixture Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Water pollutants chemical Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00924   XEOTIC Info Gene Form mRNA
                                 Classification Natural Mixture
                                 DME Modulation Water pollutants chemical up-regulates the expression of DME MPO [5]
                  Natural Product Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Gallic acid Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01309   XEOTIC Info Gene Form Protein
                                 Classification Natural Product
                                 DME Modulation Gallic acid inhibits the drug-metabolizing activity of DME MPO [2]
      Pharmaceutical Agent(s)
                  Approved/Marketed Drug Click to Show/Hide the Full List of Xenobiotics:      11 Xenobiotics
                              Abacavir Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00336   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Abacavir induces the drug-metabolizing activity of DME MPO [6]
                              Bivalirudin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00197   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Bivalirudin inhibits the drug-metabolizing activity of DME MPO [7]
                              Cisplatin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00334   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Cisplatin inhibits the expression of DME MPO [8]
                              Copper Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00834   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Copper inhibits the drug-metabolizing activity of DME MPO [9]
                              Gemcitabine Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00361   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Gemcitabine induces the drug-metabolizing activity of DME MPO [10]
                              Hydrogen peroxide Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00388   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Hydrogen peroxide induces the drug-metabolizing activity of DME MPO [11]
                              Irinotecan hydrochloride Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00301   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Irinotecan hydrochloride inhibits the expression of DME MPO [12]
                              Propylthiouracil Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00174   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Propylthiouracil inhibits the drug-metabolizing activity of DME MPO (IC50 = 2.81 microM) [13]
                              Simvastatin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00125   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Simvastatin inhibits the expression of DME MPO [14]
                              Tretinoin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00253   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Tretinoin inhibits the drug-metabolizing activity of DME MPO [15]
                              Benzoic acid Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00447   XEOTIC Info Gene Form Protein
                                 Classification Drug Marketed but not Approved by US FDA
                                 DME Modulation Benzoic acid induces the drug-metabolizing activity of DME MPO [2]
                  Drug in Phase 3 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Curcumin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00683   XEOTIC Info Gene Form Protein
                                 Classification Highest Clinical Status: Phase 3
                                 DME Modulation Curcumin inhibits the drug-metabolizing activity of DME MPO [16]
                  Drug in Phase 2 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Salicylic acid Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00546   XEOTIC Info Gene Form Protein
                                 Classification Highest Clinical Status: Phase 2/3
                                 DME Modulation Salicylic acid up-regulates the expression of DME MPO and leads to increasing the drug-metabolizing activity of this enzyme [17]
                  Drug in Phase 1 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Dinitrochlorobenzene Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00571   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 1
                                 DME Modulation Dinitrochlorobenzene inhibits the expression of DME MPO [18]
                  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 MPO [19]
                  Investigative Agent Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              4-aminobenzhydrazide Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01149   XEOTIC Info Gene Form Protein
                                 Classification Investigative Agent
                                 DME Modulation 4-aminobenzhydrazide inhibits the drug-metabolizing activity of DME MPO (IC50 = 0.3 microM) [20]
                              N-formylmethionine leucyl-phenylalanine Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01395   XEOTIC Info Gene Form mRNA
                                 Classification Investigative Agent
                                 DME Modulation N-formylmethionine leucyl-phenylalanine up-regulates the expression of DME MPO [21]
      Other Chemical Compound(s) or Element(s)
                  Chemical Compound Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Aluminum Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00839   XEOTIC Info Gene Form Protein
                                 Classification Chemical Compound
                                 DME Modulation Aluminum induces the drug-metabolizing activity of DME MPO [22]
References
1 Transcriptional and metabolic adaptation of human neurons to the mitochondrial toxicant MPP(+). Cell Death Dis. 2014 May 8;5:e1222.
2 Differentiation between stoichiometric and anticatalytic antioxidant properties of benzoic acid analogues: a structure/redox potential relationship study. Chem Biol Interact. 2013 Nov 25;206(2):194-203.
3 TNF-related apoptosis-inducing ligand (TRAIL) is expressed throughout myeloid development, resulting in a broad distribution among neutrophil granules. J Leukoc Biol. 2008 Mar;83(3):621-9.
4 Thrombin inhibits the anti-myeloperoxidase and ferroxidase functions of ceruloplasmin: relevance in rheumatoid arthritis. Free Radic Biol Med. 2015 Sep;86:279-94.
5 Human alveolar macrophages and granulocyte-macrophage colony-stimulating factor-induced monocyte-derived macrophages are resistant to H2O2 via their high basal and inducible levels of catalase activity. J Biol Chem. 2001 Jun 29;276(26):24360-4.
6 Changes in biomarkers of cardiovascular risk after a switch to abacavir in HIV-1-infected individuals receiving combination antiretroviral therapy. HIV Med. 2009 Nov;10(10):627-33.
7 Bivalirudin decreases NO bioavailability by vascular immobilization of myeloperoxidase. J Pharmacol Exp Ther. 2008 Nov;327(2):324-31.
8 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.
9 Does mercury promote lipid peroxidation? An in vitro study concerning mercury, copper, and iron in peroxidation of low-density lipoprotein. Biol Trace Elem Res. 2004 Nov;101(2):117-32.
10 Metronomic gemcitabine suppresses tumour growth, improves perfusion, and reduces hypoxia in human pancreatic ductal adenocarcinoma. Br J Cancer. 2010 Jun 29;103(1):52-60.
11 An evaluation of myeloperoxidase-mediated bio-activation of NSAIDs in promyelocytic leukemia (HL-60) cells for potential cytotoxic selectivity. Toxicol Lett. 2017 Oct 5;280:48-56.
12 In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells. Mol Cancer Ther. 2005 Jun;4(6):885-900.
13 Discovery of 2-(6-(5-chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): a highly selective mechanism-based myeloperoxidase inhibitor for the treatment of cardiovascular diseases. J Med Chem. 2015 Nov 12;58(21):8513-28.
14 High-throughput, quantitative assessment of the effects of low-dose silica nanoparticles on lung cells: grasping complex toxicity with a great depth of field. BMC Genomics. 2015 Apr 18;16:315.
15 The human placental proteome is affected by maternal smoking. Reprod Toxicol. 2016 Aug;63:22-31.
16 Intra- and extracellular antioxidant capacities of the new water-soluble form of curcumin (NDS27) on stimulated neutrophils and HL-60 cells. Chem Biol Interact. 2013 Jan 25;201(1-3):49-57.
17 Comparative effects of thiazolidinediones on in vitro P450 enzyme induction and inhibition. Drug Metab Dispos. 2003 Apr;31(4):439-46.
18 Microarray analyses in dendritic cells reveal potential biomarkers for chemical-induced skin sensitization. Mol Immunol. 2007 May;44(12):3222-33.
19 BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia. Blood. 2012 Oct 4;120(14):2843-52.
20 Evaluation of new scaffolds of myeloperoxidase inhibitors by rational design combined with high-throughput virtual screening. J Med Chem. 2012 Aug 23;55(16):7208-18.
21 SWCNTs induced autophagic cell death in human bronchial epithelial cells. Toxicol In Vitro. 2014 Apr;28(3):442-50.
22 Serum Clara cell protein as an indicator of pulmonary impairment in occupational exposure at aluminum foundry. Int J Occup Med Environ Health. 2006;19(4):211-23.

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