Details of Xenobiotics-DME Interaction (XEOTIC)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0025)
DME Name Cytochrome P450 4F2 (CYP4F2), Homo sapiens DME Info
UniProt ID
CP4F2_HUMAN
EC Number    EC: 1.14.13.30     (Click to Show/Hide the Complete EC Tree)
Oxidoreductase
Oxygen paired donor oxidoreductase
NADH/NADPH donor oxidoreductase
EC: 1.14.13.30
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 Induction
                                 XEOTIC ID XEO01305   XEOTIC Info Gene Form mRNA
                                 Classification Acute Toxic Substance
                                 DME Modulation Formaldehyde up-regulates the expression of DME CYP4F2 [1]
                  Carcinogen Click to Show/Hide the Full List of Xenobiotics:        3 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 CYP4F2 [2]
                              Ethyl methanesulfonate Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00772   XEOTIC Info Gene Form mRNA
                                 Classification Carcinogen
                                 DME Modulation Ethyl methanesulfonate up-regulates the expression of DME CYP4F2 [1]
                              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 CYP4F2 [3]
      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 CYP4F2 [4]
                              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 CYP4F2 [5]
                              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 CYP4F2 [2]
                              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 CYP4F2 [6]
                              Ketoconazole Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00251   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Ketoconazole inhibits the drug-metabolizing activity of DME CYP4F2 (IC50 = 1.6 microM) [7]
                              Vincristine Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00392   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Vincristine up-regulates the expression of DME CYP4F2 [8]
                              Demecolcine Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00466   XEOTIC Info Gene Form mRNA
                                 Classification Drug Marketed but not Approved by US FDA
                                 DME Modulation Demecolcine up-regulates the expression of DME CYP4F2 [1]
                  Drug in Phase 3 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Sulforafan Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01478   XEOTIC Info Gene Form Protein
                                 Classification Highest Clinical Status: Phase 3
                                 DME Modulation Sulforafan induces the drug-metabolizing activity of DME CYP4F2 [9]
                  Drug in Phase 2 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              Ethanol Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00539   XEOTIC Info Gene Form Protein
                                 Classification Highest Clinical Status: Phase 2
                                 DME Modulation Ethanol inhibits the drug-metabolizing activity of DME CYP4F2 [10]
                              Genistein Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00557   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 2
                                 DME Modulation Genistein up-regulates the expression of DME CYP4F2 [11]
                  Drug in Phase 1 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Aica ribonucleotide Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01190   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 1
                                 DME Modulation Aica ribonucleotide up-regulates the expression of DME CYP4F2 [11]
                  Preclinical/Patented Drug Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              TS-011 Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01386   XEOTIC Info Gene Form Protein
                                 Classification Drug in Preclinical Study
                                 DME Modulation TS-011 inhibits the drug-metabolizing activity of DME CYP4F2 [12]
                              A-769662 Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01183   XEOTIC Info Gene Form mRNA
                                 Classification Patented Pharmaceutical Agent
                                 DME Modulation A-769662 up-regulates the expression of DME CYP4F2 [11]
                  Investigative Agent Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              GW9662 Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01123   XEOTIC Info Gene Form Protein
                                 Classification Investigative Agent
                                 DME Modulation GW9662 inhibits the drug-metabolizing activity of DME CYP4F2 [10]
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 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.
3 Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma. Toxicology. 2016 Mar 28;350-352:31-9.
4 Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
5 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.
6 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.
7 CYP4F enzymes are responsible for the elimination of fingolimod (FTY720), a novel treatment of relapsing multiple sclerosis. Drug Metab Dispos. 2011 Feb;39(2):191-8.
8 Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
9 Inhibition of apoptotic signalling in spermine-treated vascular smooth muscle cells by a novel glutathione precursor. Cell Biol Int. 2010 Apr 1;34(5):503-11.
10 CYP4F2 repression and a modified alpha-tocopherol (vitamin E) metabolism are two independent consequences of ethanol toxicity in human hepatocytes. Toxicol In Vitro. 2017 Apr;40:124-133.
11 Genistein, resveratrol, and 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside induce cytochrome P450 4F2 expression through an AMP-activated protein kinase-dependent pathway. J Pharmacol Exp Ther. 2011 Apr;337(1):125-36.
12 Drug interaction study of flavonoids toward CYP3A4 and their quantitative structure activity relationship (QSAR) analysis for predicting potential effects. Toxicol Lett. 2018 Sep 15;294:27-36.

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