Details of Xenobiotics-DME Interaction (XEOTIC)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0141)
DME Name Dihydrofolate reductase (DHFR), Homo sapiens DME Info
UniProt ID
DYR_HUMAN
EC Number    EC: 1.5.1.3     (Click to Show/Hide the Complete EC Tree)
Oxidoreductase
CH-NH donor oxidoreductase
NAD/NADP acceptor oxidoreductase
EC: 1.5.1.3
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
                              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 DHFR [1]
                  Carcinogen Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              Benzo(a)pyrene Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00898   XEOTIC Info Gene Form Protein
                                 Classification Carcinogen
                                 DME Modulation Benzo(a)pyrene induces the drug-metabolizing activity of DME DHFR [2]
                              Aflatoxin M1 Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00816   XEOTIC Info Gene Form mRNA
                                 Classification Carcinogen-mycotoxin
                                 DME Modulation Aflatoxin M1 inhibits the expression of DME DHFR [3]
                  Health Hazard/Toxicant Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              1-methyl-4-phenylpyridinium Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01103   XEOTIC Info Gene Form mRNA
                                 Classification Health Hazard
                                 DME Modulation 1-methyl-4-phenylpyridinium inhibits the expression of DME DHFR [4]
                  Neurotoxin Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Alpha-cobratoxin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01594   XEOTIC Info Gene Form mRNA
                                 Classification Neurotoxin
                                 DME Modulation Alpha-cobratoxin inhibits the expression of DME DHFR [5]
      Natural Product(s), Extract(s) or Medicine(s)
                  Natural Product Click to Show/Hide the Full List of Xenobiotics:        4 Xenobiotics
                              14-deoxy-11,12-didehydroandrographolide Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01095   XEOTIC Info Gene Form mRNA
                                 Classification Natural Product
                                 DME Modulation 14-deoxy-11,12-didehydroandrographolide inhibits the expression of DME DHFR [6]
                              Epicatechin gallate Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01540   XEOTIC Info Gene Form Protein
                                 Classification Natural Product
                                 DME Modulation Epicatechin gallate inhibits the drug-metabolizing activity of DME DHFR [7]
                              Isoflavone Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01553   XEOTIC Info Gene Form mRNA
                                 Classification Natural Product
                                 DME Modulation Isoflavone inhibits the expression of DME DHFR [8]
                              Naringin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01391   XEOTIC Info Gene Form Protein
                                 Classification Natural Product
                                 DME Modulation Naringin inhibits the drug-metabolizing activity of DME DHFR [9]
      Pharmaceutical Agent(s)
                  Approved/Marketed Drug Click to Show/Hide the Full List of Xenobiotics:      22 Xenobiotics
                              Acetaminophen Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00217   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Acetaminophen up-regulates the expression of DME DHFR [10]
                              Cefazolin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00120   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Cefazolin inhibits the drug-metabolizing activity of DME DHFR [11]
                              Cefepime Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00345   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Cefepime inhibits the drug-metabolizing activity of DME DHFR [11]
                              Ceftazidime Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00237   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Ceftazidime inhibits the drug-metabolizing activity of DME DHFR [11]
                              Ceftizoxime Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00346   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Ceftizoxime inhibits the drug-metabolizing activity of DME DHFR [11]
                              Ceftriaxone Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00347   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Ceftriaxone inhibits the drug-metabolizing activity of DME DHFR [11]
                              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 DHFR [12]
                              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 DHFR [13]
                              Cytarabine Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00097   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Cytarabine up-regulates the expression of DME DHFR [14]
                              Dasatinib Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00181   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Dasatinib inhibits the expression of DME DHFR [15]
                              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 DHFR [16]
                              Dronabinol Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00115   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Dronabinol inhibits the expression of DME DHFR [17]
                              Estradiol Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00090   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Estradiol up-regulates the expression of DME DHFR [18]
                              Fluorouracil Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00037   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Fluorouracil up-regulates the expression of DME DHFR [19], [20]
                              Isotretinoin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00186   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Isotretinoin inhibits the expression of DME DHFR [21]
                              Leucovorin Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00363   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Leucovorin induces the drug-metabolizing activity of DME DHFR [22]
                              Levofloxacin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00154   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Levof DMEloxacin inhibits the drug-metabolizing activity of DME DHFR [11]
                              Mecamylamine hydrochloride Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00306   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Mecamylamine hydrochloride inhibits the drug-metabolizing activity of DME DHFR [23]
                              Methotrexate Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00366   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Methotrexate inhibits the expression of DME DHFR [24]
                              Tamoxifen Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00383   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Tamoxifen up-regulates the expression of DME DHFR [25]
                              Urethane Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00435   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Urethane inhibits the expression of DME DHFR [26]
                              Demecolcine Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00466   XEOTIC Info Gene Form mRNA
                                 Classification Drug Marketed but not Approved by US FDA
                                 DME Modulation Demecolcine inhibits the expression of DME DHFR [1]
                  Drug in Phase 3 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Epigallocatechin gallate Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00613   XEOTIC Info Gene Form Protein
                                 Classification Highest Clinical Status: Phase 3
                                 DME Modulation Epigallocatechin gallate inhibits the drug-metabolizing activity of DME DHFR [7]
                  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 Inhibition
                                 XEOTIC ID XEO01226   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 2
                                 DME Modulation Bisphenol A inhibits the expression of DME DHFR [27]
                              Ethanol Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00539   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 2
                                 DME Modulation Ethanol inhibits the expression of DME DHFR [28]
                  Preclinical/Patented Drug Click to Show/Hide the Full List of Xenobiotics:        4 Xenobiotics
                              Emodin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00692   XEOTIC Info Gene Form mRNA
                                 Classification Drug in Preclinical Study
                                 DME Modulation Emodin inhibits the expression of DME DHFR [29]
                              Ferulic acid Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00730   XEOTIC Info Gene Form Protein
                                 Classification Patented Pharmaceutical Agent
                                 DME Modulation Ferulic acid inhibits the drug-metabolizing activity of DME DHFR [11]
                              GSK-J4 Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01324   XEOTIC Info Gene Form mRNA
                                 Classification Patented Pharmaceutical Agent
                                 DME Modulation GSK-J4 inhibits the expression of DME DHFR [30]
                              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 DHFR [31]
                  Investigative Agent Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              2-desamino-2-methylaminopterin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01124   XEOTIC Info Gene Form Protein
                                 Classification Investigative Agent
                                 DME Modulation 2-desamino-2-methylaminopterin inhibits the drug-metabolizing activity of DME DHFR [32]
                              Coumestrol Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01261   XEOTIC Info Gene Form mRNA
                                 Classification Investigative Agent
                                 DME Modulation Coumestrol up-regulates the expression of DME DHFR [18]
References
1 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
2 Proteomic analysis of MCF-7 cells treated with benzo[a]pyrene, dibenzo[a,l]pyrene, coal tar extract, and diesel exhaust extract. Toxicology. 2008 Jul 10;249(1):1-10.
3 Transcriptome analysis revealed that aflatoxin M1 could cause cell cycle arrest in differentiated Caco-2 cells. Toxicol In Vitro. 2019 Sep;59:35-43.
4 Transcriptional and metabolic adaptation of human neurons to the mitochondrial toxicant MPP(+). Cell Death Dis. 2014 May 8;5:e1222.
5 Nicotine modulates the expression of a diverse set of genes in the neuronal SH-SY5Y cell line. J Biol Chem. 2003 May 2;278(18):15633-40.
6 Identification of genes involved in the regulation of 14-deoxy-11,12-didehydroandrographolide-induced toxicity in T-47D mammary cells. Food Chem Toxicol. 2012 Feb;50(2):431-44.
7 Binding of natural and synthetic polyphenols to human dihydrofolate reductase. Int J Mol Sci. 2009 Dec 18;10(12):5398-410.
8 Soy isoflavones exert differential effects on androgen responsive genes in LNCaP human prostate cancer cells. J Nutr. 2007 Apr;137(4):964-72.
9 Towards a systematic analysis of human short-chain dehydrogenases/reductases (SDR): Ligand identification and structure-activity relationships. Chem Biol Interact. 2015 Jun 5;234:114-25.
10 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.
11 Investigation of the effects of some drugs and phenolic compounds on human dihydrofolate reductase activity. J Biochem Mol Toxicol. 2015 Mar;29(3):135-9.
12 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.
13 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
14 The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
15 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.
16 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.
17 JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
18 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
19 Comparison of gene expression in HCT116 treatment derivatives generated by two different 5-fluorouracil exposure protocols. Mol Cancer. 2004 Apr 26;3:11.
20 Distamycin A and derivatives as synergic drugs in cisplatin-sensitive and -resistant ovarian cancer cells. Amino Acids. 2012 Feb;42(2-3):641-53.
21 Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
22 Leucovorin-induced resistance against FDH growth suppressor effects occurs through DHFR up-regulation. Biochem Pharmacol. 2006 Jul 14;72(2):256-66.
23 Establishment of a novel model for studying the effects of extracts of Chinese herb medicine on human type II 5alpha-reductase in vitro. Yakugaku Zasshi. 2010 Sep;130(9):1207-14.
24 Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
25 Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
26 Toxicogenomics of the flame retardant tris (2-butoxyethyl) phosphate in HepG2 cells using RNA-seq. Toxicol In Vitro. 2018 Feb;46:178-188.
27 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.
28 Gene expression signatures after ethanol exposure in differentiating embryoid bodies. Toxicol In Vitro. 2018 Feb;46:66-76.
29 Gene expression alteration during redox-dependent enhancement of arsenic cytotoxicity by emodin in HeLa cells. Cell Res. 2005 Jul;15(7):511-22.
30 Inhibition of histone H3K27 demethylases selectively modulates inflammatory phenotypes of natural killer cells. J Biol Chem. 2018 Feb 16;293(7):2422-2437.
31 A low-molecular-weight compound K7174 represses hepcidin: possible therapeutic strategy against anemia of chronic disease. PLoS One. 2013 Sep 27;8(9):e75568.
32 Biochemical and biological studies on 2-desamino-2-methylaminopterin, an antifolate the polyglutamates of which are more potent than the monoglutamate against three key enzymes of folate metabolism. Cancer Res. 1992 Apr 15;52(8):2148-55.

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