Details of Xenobiotics-DME Interaction (XEOTIC)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0083)
DME Name Methylenetetrahydrofolate reductase (MTHFR), Homo sapiens DME Info
UniProt ID
MTHR_HUMAN
EC Number    EC: 1.5.1.20     (Click to Show/Hide the Complete EC Tree)
Oxidoreductase
CH-NH donor oxidoreductase
NAD/NADP acceptor oxidoreductase
EC: 1.5.1.20
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:        1 Xenobiotics
                              Butyraldehyde Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00999   XEOTIC Info Gene Form mRNA
                                 Classification Health Hazard
                                 DME Modulation Butyraldehyde inhibits the expression of DME MTHFR [1]
      Pharmaceutical Agent(s)
                  Approved/Marketed Drug Click to Show/Hide the Full List of Xenobiotics:        7 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 MTHFR [2]
                              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 MTHFR [3]
                              Methotrexate Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00366   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Methotrexate up-regulates the expression of DME MTHFR [4]
                              Raloxifene hydrochloride Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00126   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Raloxifene hydrochloride inhibits the expression of DME MTHFR [5], [6]
                              Testosterone Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00095   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Testosterone induces the drug-metabolizing activity of DME MTHFR [7]
                              Tretinoin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00253   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Tretinoin inhibits the expression of DME MTHFR [8]
                              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 MTHFR [9], [10]
                  Drug in Phase 2 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        1 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 MTHFR [11]
                  Drug in Phase 1 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Homocysteine Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01331   XEOTIC Info Gene Form Protein
                                 Classification Highest Clinical Status: Phase 1
                                 DME Modulation Homocysteine induces the drug-metabolizing activity of DME MTHFR [12]
                  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 MTHFR [13]
                              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 MTHFR [14]
      Other Chemical Compound(s) or Element(s)
                  Chemical Compound Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Pentanal Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01034   XEOTIC Info Gene Form mRNA
                                 Classification Chemical Compound
                                 DME Modulation Pentanal inhibits the expression of DME MTHFR [15]
References
1 Integrated analysis of microRNA and mRNA expression profiles highlights aldehyde-induced inflammatory responses in cells relevant for lung toxicity. Toxicology. 2015 Aug 6;334:111-21.
2 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
3 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
4 Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
5 Quercetin-induced downregulation of phospholipase D1 inhibits proliferation and invasion in U87 glioma cells. Biochem Biophys Res Commun. 2011 Sep 9;412(4):710-5.
6 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
7 The chemopreventive effect of taxifolin is exerted through ARE-dependent gene regulation. Biol Pharm Bull. 2007 Jun;30(6):1074-9.
8 Assessment of a 72-hour repeated exposure to Swedish snus extract and total particulate matter from 3R4F cigarette smoke on gingival organotypic cultures. Food Chem Toxicol. 2019 Mar;125:252-270.
9 MAPK signaling pathways modulate IL-1beta expression in human keratinocytes. Arch Biochem Biophys. 2004 Apr 1;424(1):112-8.
10 ERK kinase inhibition stabilizes the aryl hydrocarbon receptor: implications for transcriptional activation and protein degradation. J Biol Chem. 2005 Feb 11;280(6):4350-9.
11 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.
12 Homocysteine modulates the effect of simvastatin on expression of ApoA-I and NF-kappaB/iNOS. Cardiovasc Res. 2008 Oct 1;80(1):151-8.
13 BET bromodomain protein inhibition is a therapeutic option for medulloblastoma. Oncotarget. 2013 Nov;4(11):2080-95.
14 Inhibition of histone H3K27 demethylases selectively modulates inflammatory phenotypes of natural killer cells. J Biol Chem. 2018 Feb 16;293(7):2422-2437.
15 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.

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