Details of Xenobiotics-DME Interaction (XEOTIC)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0168)
DME Name Neprilysin (MME), Homo sapiens DME Info
UniProt ID
NEP_HUMAN
EC Number    EC: 3.4.24.11     (Click to Show/Hide the Complete EC Tree)
Hydrolases
Peptidase
Metallopeptidase
EC: 3.4.24.11
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
                              Mercury Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01509   XEOTIC Info Gene Form Protein
                                 Classification Acute Toxic Substance
                                 DME Modulation Mercury inhibits the drug-metabolizing activity of DME MME [1]
                  Carcinogen Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              Benzo(a)pyrene Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00898   XEOTIC Info Gene Form mRNA
                                 Classification Carcinogen
                                 DME Modulation Benzo(a)pyrene inhibits the expression of DME MME [2]
                              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 MME [3]
                  Health Hazard/Toxicant Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              Diethylhexyl phthalate Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01004   XEOTIC Info Gene Form Protein
                                 Classification Health Hazard
                                 DME Modulation Diethylhexyl phthalate inhibits the drug-metabolizing activity of DME MME [4]
                              Lead Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01505   XEOTIC Info Gene Form Protein
                                 Classification Health Hazard
                                 DME Modulation Lead inhibits the expression of DME MME and leads to decreasing the drug-metabolizing activity of this enzyme [5]
      Natural Product(s), Extract(s) or Medicine(s)
                  Natural Mixture Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Tobacco smoke pollution Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00821   XEOTIC Info Gene Form Protein
                                 Classification Natural Mixture
                                 DME Modulation Tobacco smoke pollution inhibits the drug-metabolizing activity of DME MME [6]
      Pharmaceutical Agent(s)
                  Approved/Marketed Drug Click to Show/Hide the Full List of Xenobiotics:      10 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 MME [7]
                              Bicalutamide Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00009   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Bicalutamide up-regulates the expression of DME MME [8]
                              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 MME [9]
                              Doxorubicin hydrochloride Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00292   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Doxorubicin hydrochloride inhibits the drug-metabolizing activity of DME MME [10]
                              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 MME [11]
                              Fulvestrant Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00147   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Fulvestrant up-regulates the expression of DME MME [12]
                              Nicotine polacrilex Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00312   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Nicotine polacrilex up-regulates the expression of DME MME [13]
                              Progesterone Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00094   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Progesterone up-regulates the expression of DME MME [14]
                              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 MME [15], [16]
                              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 MME [17]
                  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 mRNA
                                 Classification Highest Clinical Status: Phase 3
                                 DME Modulation Curcumin inhibits the expression of DME MME [18]
                  Drug in Phase 2 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        6 Xenobiotics
                              Acyline Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00674   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 2
                                 DME Modulation Acyline inhibits the expression of DME MME [19]
                              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 MME [20]
                              Candoxatrilat Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00631   XEOTIC Info Gene Form Protein
                                 Classification Highest Clinical Status: Phase 2
                                 DME Modulation Candoxatrilat inhibits the drug-metabolizing activity of DME MME (IC50 = 0.0078 microM) [21]
                              MS-275 Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00581   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 2
                                 DME Modulation MS-275 up-regulates the expression of DME MME [22], [23]
                              Omapatrilat Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00638   XEOTIC Info Gene Form Protein
                                 Classification Highest Clinical Status: Phase 2
                                 DME Modulation Omapatrilat inhibits the drug-metabolizing activity of DME MME (Ki = 0.009 microM) [24]
                              ZD4054 Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00669   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 2
                                 DME Modulation ZD4054 inhibits the expression of DME MME [25]
                  Drug in Phase 1 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        3 Xenobiotics
                              Sodium arsenite Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00632   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 1
                                 DME Modulation Sodium arsenite up-regulates the expression of DME MME [26]
                              Tetradecanoylphorbol acetate Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00599   XEOTIC Info Gene Form Protein
                                 Classification Highest Clinical Status: Phase 1
                                 DME Modulation Tetradecanoylphorbol acetate inhibits the drug-metabolizing activity of DME MME [27]
                              Trichostatin A Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01492   XEOTIC Info Gene Form Protein
                                 Classification Highest Clinical Status: Phase 1
                                 DME Modulation Trichostatin A induces the drug-metabolizing activity of DME MME [28]
                  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 MME [29]
                  Investigative Agent Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Thiorphan Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01484   XEOTIC Info Gene Form Protein
                                 Classification Investigative Agent
                                 DME Modulation Thiorphan inhibits the drug-metabolizing activity of DME MME (IC50 = 0.001 microM) [30]
References
1 Polycyclic aromatic hydrocarbon/metal mixtures: effect on PAH induction of CYP1A1 in human HEPG2 cells. Drug Metab Dispos. 2001 Jul;29(7):999-1006.
2 Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
3 Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma. Toxicology. 2016 Mar 28;350-352:31-9.
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 In vitro Pb exposure disturbs the balance between Abeta production and elimination: the role of AbetaPP and neprilysin. Neurotoxicology. 2011 Jun;32(3):300-6.
6 Inhibition of human aromatase complex (CYP19) by antiepileptic drugs. Toxicol In Vitro. 2008 Feb;22(1):146-53.
7 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
8 Casodex treatment induces hypoxia-related gene expression in the LNCaP prostate cancer progression model. BMC Urol. 2005 Mar 24;5:5.
9 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.
10 PMA and doxorubicin decrease viability, MTT activity and expression of CD10 marker on NALM-1 leukemic cells. Immunopharmacol Immunotoxicol. 2006;28(3):411-20.
11 Bisphenol A effects on gene expression in adipocytes from children: association with metabolic disorders. J Mol Endocrinol. 2015 Jun;54(3):289-303.
12 Analysis of estrogen agonism and antagonism of tamoxifen, raloxifene, and ICI182780 in endometrial cancer cells: a putative role for the epidermal growth factor receptor ligand amphiregulin. J Soc Gynecol Investig. 2005 Oct;12(7):e55-67.
13 Keratinocyte gene expression profiles discriminate sensitizing and irritating compounds. Toxicol Sci. 2010 Sep;117(1):81-9.
14 Tissue-specific, inducible, and hormonal control of the human UDP-glucuronosyltransferase-1 (UGT1) locus. J Biol Chem. 2005 Nov 11;280(45):37547-57.
15 Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
16 Steroid profiling in H295R cells to identify chemicals potentially disrupting the production of adrenal steroids. Toxicology. 2017 Apr 15;381:51-63.
17 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
18 Gene-expression profiling during curcumin-induced apoptosis reveals downregulation of CXCR4. Exp Hematol. 2007 Jan;35(1):84-95.
19 Intraprostatic androgens and androgen-regulated gene expression persist after testosterone suppression: therapeutic implications for castration-resistant prostate cancer. Cancer Res. 2007 May 15;67(10):5033-41.
20 Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells. Toxicol Appl Pharmacol. 2010 Oct 15;248(2):111-21.
21 Synthesis and evaluation of heteroarylalanine diacids as potent and selective neutral endopeptidase inhibitors. Bioorg Med Chem Lett. 2011 Jun 1;21(11):3404-6.
22 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.
23 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
24 Phosphinic tripeptides as dual angiotensin-converting enzyme C-domain and endothelin-converting enzyme-1 inhibitors. J Med Chem. 2010 Jan 14;53(1):208-20.
25 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
26 Global alteration of gene expression in human keratinocytes by inorganic arsenic. Carcinogenesis. 2003 Apr;24(4):747-56.
27 Two persistent organic pollutants which act through different xenosensors (alpha-endosulfan and 2,3,7,8 tetrachlorodibenzo-p-dioxin) interact in a mixture and downregulate multiple genes involved in human hepatocyte lipid and glucose metabolism. Biochimie. 2015 Sep;116:79-91.
28 High concentrations of retinoids induce differentiation and late apoptosis in pancreatic cancer cells in vitro. Cancer Biol Ther. 2005 May;4(5):602-11.
29 Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
30 Imidazole-derived 2-[N-carbamoylmethyl-alkylamino]acetic acids, substrate-dependent modulators of insulin-degrading enzyme in amyloid-beta hydrolysis. Eur J Med Chem. 2014 May 22;79:184-93.

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