Details of Xenobiotics-DME Interaction (XEOTIC)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0133)
DME Name Dipeptidyl peptidase IV (DPP4), Homo sapiens DME Info
UniProt ID
DPP4_HUMAN
EC Number    EC: 3.4.14.5     (Click to Show/Hide the Complete EC Tree)
Hydrolases
Peptidase
Di/tripeptidyl peptidase
EC: 3.4.14.5
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)
      Fungicide(s), Herbicide(s) or Insecticide(s)
                  Herbicide Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Diuron Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00973   XEOTIC Info Gene Form mRNA
                                 Classification Herbicide
                                 DME Modulation Diuron up-regulates the expression of DME DPP4 [1]
                  Pesticide/Insecticide Click to Show/Hide the Full List of Xenobiotics:        1 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 DPP4 [2]
      Health or Environmental Toxicant(s)
                  Acute Toxic Substance Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Formaldehyde Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01305   XEOTIC Info Gene Form mRNA
                                 Classification Acute Toxic Substance
                                 DME Modulation Formaldehyde inhibits the expression of DME DPP4 [3]
                  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 DPP4 [4]
                              Ethyl methanesulfonate Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00772   XEOTIC Info Gene Form mRNA
                                 Classification Carcinogen
                                 DME Modulation Ethyl methanesulfonate inhibits the expression of DME DPP4 [3]
      Pharmaceutical Agent(s)
                  Approved/Marketed Drug Click to Show/Hide the Full List of Xenobiotics:      15 Xenobiotics
                              Acetaminophen Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00217   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Acetaminophen induces the drug-metabolizing activity of DME DPP4 [5]
                              Adenosine Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00134   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Adenosine inhibits the drug-metabolizing activity of DME DPP4 [6]
                              Arsenic trioxide Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00339   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Arsenic trioxide inhibits the expression of DME DPP4 [7], [8]
                              Azathioprine Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00007   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Azathioprine inhibits the expression of DME DPP4 [9]
                              Calcitriol Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00184   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Calcitriol up-regulates the expression of DME DPP4 [10]
                              Copper sulfate Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00117   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Copper sulfate inhibits the expression of DME DPP4 [11]
                              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 DPP4 [12]
                              Dasatinib Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00181   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Dasatinib up-regulates the expression of DME DPP4 [13]
                              Doxorubicin hydrochloride Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00292   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Doxorubicin hydrochloride inhibits the expression of DME DPP4 [14]
                              Mdv-3100 Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00196   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Mdv-3100 inhibits the drug-metabolizing activity of DME DPP4 [15]
                              Progesterone Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00094   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Progesterone induces the drug-metabolizing activity of DME DPP4 [16], [17]
                              Saxagliptin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00381   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Saxagliptin inhibits the drug-metabolizing activity of DME DPP4 (IC50 = 0.0006 microM) [18]
                              Sitagliptin phosphate Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00252   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Sitagliptin phosphate inhibits the drug-metabolizing activity of DME DPP4 (IC50 = 0.0035 microM) [19]
                              Vincristine Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00392   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Vincristine inhibits the expression of DME DPP4 [20], [21]
                              Vildagliptin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00445   XEOTIC Info Gene Form Protein
                                 Classification Drug Marketed but not Approved by US FDA
                                 DME Modulation Vildagliptin inhibits the drug-metabolizing activity of DME DPP4 (IC50 = 0.00058 microM) [19]
                  Drug in Phase 3 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Triclosan Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00560   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 3
                                 DME Modulation Triclosan up-regulates the expression of DME DPP4 [22]
                  Drug in Phase 2 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              Bisphenol A Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01226   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 2
                                 DME Modulation Bisphenol A up-regulates the expression of DME DPP4 [23], [24]
                              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 DPP4 [25]
                  Drug in Phase 1 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              Dihydrotestosterone Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00536   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 1
                                 DME Modulation Dihydrotestosterone up-regulates the expression of DME DPP4 [26]
                              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 DPP4 [27]
                  Preclinical/Patented Drug Click to Show/Hide the Full List of Xenobiotics:        2 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 DPP4 [28]
                              K-7174 Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01348   XEOTIC Info Gene Form mRNA
                                 Classification Patented Pharmaceutical Agent
                                 DME Modulation K-7174 inhibits the expression of DME DPP4 [29]
References
1 Diuron metabolites and urothelial cytotoxicity: in vivo, in vitro and molecular approaches. Toxicology. 2013 Dec 15;314(2-3):238-46.
2 Molecular mechanisms of discrotophos-induced toxicity in HepG2 cells: The role of CSA in oxidative stress. Food Chem Toxicol. 2017 May;103:253-260.
3 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
4 Genome-wide transcriptional and functional analysis of human T lymphocytes treated with benzo[alpha]pyrene. Int J Mol Sci. 2018 Nov 17;19(11).
5 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
6 Adenosine downregulates DPPIV on HT-29 colon cancer cells by stimulating protein tyrosine phosphatase(s) and reducing ERK1/2 activity via a novel pathway. Am J Physiol Cell Physiol. 2006 Sep;291(3):C433-44.
7 Grouping of histone deacetylase inhibitors and other toxicants disturbing neural crest migration by transcriptional profiling. Neurotoxicology. 2015 Sep;50:56-70.
8 Effect of subchronic exposure to inorganic arsenic on the structure and function of the intestinal epithelium. Toxicol Lett. 2018 Apr;286:80-88.
9 Severe villus atrophy and chronic malabsorption induced by azathioprine. Gastroenterology. 2003 Jun;124(7):1950-7.
10 Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
11 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
12 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.
13 Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
14 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
15 Mangifera indica Lextract and mangiferin modulate cytochrome P450 and UDP-glucuronosyltransferase enzymes in primary cultures of human hepatocytes. Phytother Res. 2013 May;27(5):745-52.
16 Tissue-specific, inducible, and hormonal control of the human UDP-glucuronosyltransferase-1 (UGT1) locus. J Biol Chem. 2005 Nov 11;280(45):37547-57.
17 Induction of the UDP-glucuronosyltransferase 1A1 during the perinatal period can cause neurodevelopmental toxicity. Mol Pharmacol. 2016 Sep;90(3):265-74.
18 Structure-activity relationship studies on isoindoline inhibitors of dipeptidyl peptidases 8 and 9 (DPP8, DPP9): is DPP8-selectivity an attainable goal? J Med Chem. 2011 Aug 25;54(16):5737-46.
19 2-({6-[(3R)-3-amino-3-methylpiperidine-1-yl]-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-5H-pyrrolo[3,2-d]pyrimidine-5-yl}methyl)-4-fluorobenzonitrile (DSR-12727): a potent, orally active dipeptidyl peptidase IV inhibitor without mechanism-based inactivation of CYP3A. Bioorg Med Chem. 2011 Sep 15;19(18):5490-9.
20 Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
21 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
22 Effects of low dose treatment of tributyltin on the regulation of estrogen receptor functions in MCF-7 cells. Toxicol Appl Pharmacol. 2013 Jun 1;269(2):176-86.
23 Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
24 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
25 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.
26 LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
27 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
28 Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
29 A low-molecular-weight compound K7174 represses hepcidin: possible therapeutic strategy against anemia of chronic disease. PLoS One. 2013 Sep 27;8(9):e75568.

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