Details of Xenobiotics-DME Interaction (XEOTIC)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0031)
DME Name Cytochrome P450 2J2 (CYP2J2), Homo sapiens DME Info
UniProt ID
CP2J2_HUMAN
EC Number    EC: 1.14.14.24     (Click to Show/Hide the Complete EC Tree)
Oxidoreductase
Oxygen paired donor oxidoreductase
Flavin/flavoprotein donor oxidoreductase
EC: 1.14.14.24
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
                              Atrazine Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00969   XEOTIC Info Gene Form mRNA
                                 Classification Herbicide
                                 DME Modulation Atrazine up-regulates the expression of DME CYP2J2 [1]
      Health or Environmental Toxicant(s)
                  Carcinogen Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Benzo(a)pyrene Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00898   XEOTIC Info Gene Form mRNA
                                 Classification Carcinogen
                                 DME Modulation Benzo(a)pyrene up-regulates the expression of DME CYP2J2 [2]
                  Health Hazard/Toxicant Click to Show/Hide the Full List of Xenobiotics:        3 Xenobiotics
                              Butyraldehyde Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00999   XEOTIC Info Gene Form mRNA
                                 Classification Health Hazard
                                 DME Modulation Butyraldehyde up-regulates the expression of DME CYP2J2 [3]
                              Diethylhexyl phthalate Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01004   XEOTIC Info Gene Form mRNA
                                 Classification Health Hazard
                                 DME Modulation Diethylhexyl phthalate inhibits the expression of DME CYP2J2 [4]
                              Glycidamide Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01009   XEOTIC Info Gene Form mRNA
                                 Classification Health Hazard
                                 DME Modulation Glycidamide inhibits the expression of DME CYP2J2 [5]
      Natural Product(s), Extract(s) or Medicine(s)
                  Natural Product Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              Alpha-naphthoflavone Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01192   XEOTIC Info Gene Form Protein
                                 Classification Natural Product
                                 DME Modulation Alpha-naphthof DMElavone inhibits the drug-metabolizing activity of DME CYP2J2 [6]
                              Salvianolic acid C Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00861   XEOTIC Info Gene Form Protein
                                 Classification Natural Product
                                 DME Modulation Salvianolic acid C inhibits the drug-metabolizing activity of DME CYP2J2 [7]
      Pharmaceutical Agent(s)
                  Approved/Marketed Drug Click to Show/Hide the Full List of Xenobiotics:      22 Xenobiotics
                              Acetaminophen Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00217   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Acetaminophen inhibits the drug-metabolizing activity of DME CYP2J2 (IC50 > 50 microM) [8]
                              Amiodarone hydrochloride Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00277   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Amiodarone hydrochloride up-regulates the expression of DME CYP2J2 [9]
                              Amlodipine Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00338   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Amlodipine inhibits the drug-metabolizing activity of DME CYP2J2 [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 CYP2J2 [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 CYP2J2 [12], [13]
                              Danazol Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00118   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Danazol inhibits the drug-metabolizing activity of DME CYP2J2 (IC50 < 0.1 microM) [14]
                              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 CYP2J2 [15]
                              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 CYP2J2 [16]
                              Felodipine Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00245   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Felodipine inhibits the drug-metabolizing activity of DME CYP2J2 [10]
                              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 CYP2J2 [6]
                              Nicardipine hydrochloride Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00311   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Nicardipine hydrochloride inhibits the drug-metabolizing activity of DME CYP2J2 (IC50 = 1.69 microM) [8]
                              Nifedipine Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00066   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Nifedipine inhibits the drug-metabolizing activity of DME CYP2J2 (IC50 = 3.06 microM) [8]
                              Rosiglitazone Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00380   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Rosiglitazone up-regulates the expression of DME CYP2J2 [17]
                              Telmisartan Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00271   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Telmisartan inhibits the drug-metabolizing activity of DME CYP2J2 (IC50 = 0.42 microM) [8]
                              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 CYP2J2 [18]
                              Troglitazone Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00086   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Troglitazone inhibits the expression of DME CYP2J2 [19]
                              Urethane Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00435   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Urethane up-regulates the expression of DME CYP2J2 [20]
                              Azelnidipine Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00491   XEOTIC Info Gene Form Protein
                                 Classification Drug Marketed but not Approved by US FDA
                                 DME Modulation Azelnidipine inhibits the drug-metabolizing activity of DME CYP2J2 [10]
                              Benidipine Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00438   XEOTIC Info Gene Form Protein
                                 Classification Drug Marketed but not Approved by US FDA
                                 DME Modulation Benidipine inhibits the drug-metabolizing activity of DME CYP2J2 [10]
                              Ebastine Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00496   XEOTIC Info Gene Form Protein
                                 Classification Drug Marketed but not Approved by US FDA
                                 DME Modulation Ebastine inhibits the drug-metabolizing activity of DME CYP2J2 [6]
                              Efonidipine Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00467   XEOTIC Info Gene Form Protein
                                 Classification Drug Marketed but not Approved by US FDA
                                 DME Modulation Efonidipine inhibits the drug-metabolizing activity of DME CYP2J2 [10]
                              Nitrendipine Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00514   XEOTIC Info Gene Form Protein
                                 Classification Drug Marketed but not Approved by US FDA
                                 DME Modulation Nitrendipine inhibits the drug-metabolizing activity of DME CYP2J2 [21]
                  Drug in Phase 3 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        3 Xenobiotics
                              Cilnidipine Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00563   XEOTIC Info Gene Form Protein
                                 Classification Highest Clinical Status: Phase 3
                                 DME Modulation Cilnidipine inhibits the drug-metabolizing activity of DME CYP2J2 [10]
                              Delapril Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00552   XEOTIC Info Gene Form Protein
                                 Classification Highest Clinical Status: Phase 3
                                 DME Modulation Delapril inhibits the drug-metabolizing activity of DME CYP2J2 [10]
                              Manidipine Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00567   XEOTIC Info Gene Form Protein
                                 Classification Highest Clinical Status: Phase 3
                                 DME Modulation Manidipine inhibits the drug-metabolizing activity of DME CYP2J2 [22]
                  Drug in Phase 1 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              Butylated hydroxytoluene Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00601   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 1
                                 DME Modulation Butylated hydroxytoluene up-regulates the expression of DME CYP2J2 [23]
                              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 CYP2J2 [24]
                  Preclinical/Patented Drug Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              MRK-003 Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00721   XEOTIC Info Gene Form Protein
                                 Classification Drug in Preclinical Study
                                 DME Modulation MRK-003 inhibits the drug-metabolizing activity of DME CYP2J2 [25]
                  Drug Marketed but Withdrawn from Market Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Terfenadine Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00523   XEOTIC Info Gene Form Protein
                                 Classification Drug Marketed but Withdrawn from Market
                                 DME Modulation Terfenadine inhibits the drug-metabolizing activity of DME CYP2J2 (IC50 = 1.13 microM) [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 Induction
                                 XEOTIC ID XEO01034   XEOTIC Info Gene Form mRNA
                                 Classification Chemical Compound
                                 DME Modulation Pentanal up-regulates the expression of DME CYP2J2 [26]
References
1 Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
2 New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
3 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.
4 Long-term di (2-ethylhexyl)-phthalate exposure promotes proliferation and survival of HepG2 cells via activation of NFB. Toxicol In Vitro. 2017 Aug;42:86-92.
5 Expression profile of human cells in culture exposed to glycidamide, a reactive metabolite of the heat-induced food carcinogen acrylamide. Toxicology. 2007 Oct 30;240(1-2):111-24.
6 In vitro inhibition of human small intestinal and liver microsomal astemizole O-demethylation: different contribution of CYP2J2 in the small intestine and liver. Xenobiotica. 2003 Jun;33(6):615-23.
7 Molecular Insights into Human Monoamine Oxidase B Inhibition by the Glitazone Anti-Diabetes Drugs. ACS Med Chem Lett. 2011 Oct 15;3(1):39-42.
8 Discovery and characterization of novel, potent, and selective cytochrome P450 2J2 inhibitors. Drug Metab Dispos. 2013 Jan;41(1):60-71.
9 Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
10 Inhibitory effects of antihypertensive drugs on human cytochrome P450 2J2 activity: Potent inhibition by azelnidipine and manidipine. Chem Biol Interact. 2019 Jun 1;306:1-9.
11 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
12 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.
13 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
14 Identifying a selective substrate and inhibitor pair for the evaluation of CYP2J2 activity. Drug Metab Dispos. 2012 May;40(5):943-51.
15 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.
16 Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
17 Expression and inducibility of cytochrome P450s (CYP1A1, 2B6, 2E1, 3A4) in human cord blood CD34(+) stem cell-derived differentiating neuronal cells. Toxicol Sci. 2012 Oct;129(2):392-410.
18 Comparison of cellular and transcriptomic effects between electronic cigarette vapor and cigarette smoke in human bronchial epithelial cells. Toxicol In Vitro. 2017 Dec;45(Pt 3):417-425.
19 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
20 Endocrine disruption potentials of organophosphate flame retardants and related mechanisms in H295R and MVLN cell lines and in zebrafish. Aquat Toxicol. 2012 Jun 15;114-115:173-81.
21 Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s. Drug Metab Dispos. 2001 Jan;29(1):30-5.
22 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.
23 Activity, inhibition, and induction of cytochrome P450 2J2 in adult human primary cardiomyocytes. Drug Metab Dispos. 2013 Dec;41(12):2087-94.
24 Simvastatin inactivates beta1-integrin and extracellular signal-related kinase signaling and inhibits cell proliferation in head and neck squamous cell carcinoma cells. Cancer Sci. 2007 Jun;98(6):890-9.
25 Monomethylarsonous acid inhibited endogenous cholesterol biosynthesis in human skin fibroblasts. Toxicol Appl Pharmacol. 2014 May 15;277(1):21-9.
26 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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