Details of Xenobiotics-DME Interaction (XEOTIC)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0087)
DME Name Aldo-keto reductase 1B1 (AKR1B1), Homo sapiens DME Info
UniProt ID
ALDR_HUMAN
EC Number    EC: 1.1.1.21     (Click to Show/Hide the Complete EC Tree)
Oxidoreductase
CH-OH donor oxidoreductase
NAD/NADP oxidoreductase
EC: 1.1.1.21
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:        2 Xenobiotics
                              Cadmium Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01503   XEOTIC Info Gene Form mRNA
                                 Classification Acute Toxic Substance
                                 DME Modulation Cadmium inhibits the expression of DME AKR1B1 [1]
                              Nickel chloride Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01397   XEOTIC Info Gene Form mRNA
                                 Classification Acute Toxic Substance
                                 DME Modulation Nickel chloride inhibits the expression of DME AKR1B1 [2]
                  Carcinogen Click to Show/Hide the Full List of Xenobiotics:        3 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 AKR1B1 [3]
                              Dimethyl nitrosamine Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01006   XEOTIC Info Gene Form mRNA
                                 Classification Carcinogen
                                 DME Modulation Dimethyl nitrosamine inhibits the expression of DME AKR1B1 [1]
                              Aflatoxin B1 Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00806   XEOTIC Info Gene Form mRNA
                                 Classification Carcinogen-mycotoxin
                                 DME Modulation Aflatoxin B1 up-regulates the expression of DME AKR1B1 [4], [5]
                  Environmental Pollutant Click to Show/Hide the Full List of Xenobiotics:        3 Xenobiotics
                              Antimony potassium tartrate Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01201   XEOTIC Info Gene Form mRNA
                                 Classification Environmental Pollutant
                                 DME Modulation Antimony potassium tartrate up-regulates the expression of DME AKR1B1 [6]
                              Hexyl cinnamic aldehyde Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00985   XEOTIC Info Gene Form mRNA
                                 Classification Environmental Pollutant
                                 DME Modulation Hexyl cinnamic aldehyde up-regulates the expression of DME AKR1B1 [7]
                              Sodium arsenate Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01023   XEOTIC Info Gene Form mRNA
                                 Classification Environmental Pollutant
                                 DME Modulation Sodium arsenate up-regulates the expression of DME AKR1B1 [8]
                  Health Hazard/Toxicant Click to Show/Hide the Full List of Xenobiotics:        3 Xenobiotics
                              N-hexane Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01016   XEOTIC Info Gene Form mRNA
                                 Classification Health and Environmental Toxicant
                                 DME Modulation N-hexane up-regulates the expression of DME AKR1B1 [9]
                              CD-437 Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01241   XEOTIC Info Gene Form mRNA
                                 Classification Health Hazard
                                 DME Modulation CD-437 inhibits the expression of DME AKR1B1 [10]
                              Pirinixic acid Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01433   XEOTIC Info Gene Form Protein
                                 Classification Health Hazard
                                 DME Modulation Pirinixic acid inhibits the drug-metabolizing activity of DME AKR1B1 [11]
      Pharmaceutical Agent(s)
                  Approved/Marketed Drug Click to Show/Hide the Full List of Xenobiotics:        9 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 AKR1B1 [12]
                              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 AKR1B1 [1]
                              Bortezomib Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00159   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Bortezomib induces the drug-metabolizing activity of DME AKR1B1 [13]
                              Cisplatin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00334   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Cisplatin inhibits the drug-metabolizing activity of DME AKR1B1 [14]
                              Cyclosporine Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00241   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Cyclosporine up-regulates the expression of DME AKR1B1 [15]
                              Disulfiram Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00028   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Disulfiram up-regulates the expression of DME AKR1B1 [7]
                              Doxorubicin hydrochloride Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00292   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Doxorubicin hydrochloride up-regulates the expression of DME AKR1B1 [16]
                              Sulindac Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00177   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Sulindac inhibits the drug-metabolizing activity of DME AKR1B1 (IC50 = 0.374 microM) [17]
                              Benzoic acid Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00447   XEOTIC Info Gene Form mRNA
                                 Classification Drug Marketed but not Approved by US FDA
                                 DME Modulation Benzoic acid up-regulates the expression of DME AKR1B1 [7]
                  Drug in Phase 3 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              Exisulind Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00659   XEOTIC Info Gene Form Protein
                                 Classification Highest Clinical Status: Phase 3
                                 DME Modulation Exisulind inhibits the drug-metabolizing activity of DME AKR1B1 [18]
                              Sorbinil Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00630   XEOTIC Info Gene Form Protein
                                 Classification Highest Clinical Status: Phase 3
                                 DME Modulation Sorbinil inhibits the drug-metabolizing activity of DME AKR1B1 (IC50 = 0.067 microM) [19]
                  Drug in Phase 2 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Antimony Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00657   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 2
                                 DME Modulation Antimony inhibits the expression of DME AKR1B1 [1]
                  Drug in Phase 1 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        4 Xenobiotics
                              Dinitrochlorobenzene Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00571   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 1
                                 DME Modulation Dinitrochlorobenzene up-regulates the expression of DME AKR1B1 [7]
                              Methyl salicylate Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01376   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 1
                                 DME Modulation Methyl salicylate up-regulates the expression of DME AKR1B1 [20]
                              Phenethyl caffeate Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01233   XEOTIC Info Gene Form Protein
                                 Classification Highest Clinical Status: Phase 1
                                 DME Modulation Phenethyl caffeate inhibits the drug-metabolizing activity of DME AKR1B1 (IC50 = 0.57 microM) [21]
                              SNK-860 Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00628   XEOTIC Info Gene Form Protein
                                 Classification Highest Clinical Status: Phase 1
                                 DME Modulation SNK-860 inhibits the drug-metabolizing activity of DME AKR1B1 (IC50 = 0.009 microM) [22]
                  Preclinical/Patented Drug Click to Show/Hide the Full List of Xenobiotics:        3 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 AKR1B1 [23]
                              Zopolrestat Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00688   XEOTIC Info Gene Form Protein
                                 Classification Drug in Preclinical Study
                                 DME Modulation Zopolrestat inhibits the drug-metabolizing activity of DME AKR1B1 (IC50 = 0.0019 microM) [24]
                              Eugenol Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00885   XEOTIC Info Gene Form mRNA
                                 Classification Patented Pharmaceutical Agent
                                 DME Modulation Eugenol up-regulates the expression of DME AKR1B1 [7]
                  Investigative Agent Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              Isopropanol Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01128   XEOTIC Info Gene Form mRNA
                                 Classification Investigative Agent
                                 DME Modulation Isopropanol up-regulates the expression of DME AKR1B1 [7]
                              MG-132 Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01219   XEOTIC Info Gene Form mRNA
                                 Classification Investigative Agent
                                 DME Modulation MG-132 up-regulates the expression of DME AKR1B1 [13]
References
1 Classification of heavy-metal toxicity by human DNA microarray analysis. Environ Sci Technol. 2007 May 15;41(10):3769-74.
2 Patients with atopic dermatitis have attenuated and distinct contact hypersensitivity responses to common allergens in skin. J Allergy Clin Immunol. 2015 Mar;135(3):712-20.
3 New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
4 Identification of early target genes of aflatoxin B1 in human hepatocytes, inter-individual variability and comparison with other genotoxic compounds. Toxicol Appl Pharmacol. 2012 Jan 15;258(2):176-87.
5 Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma. Toxicology. 2016 Mar 28;350-352:31-9.
6 Parallel responses of human epidermal keratinocytes to inorganic SbIII and AsIII. Environ Chem. 2016;13(6):963-970.
7 Keratinocyte gene expression profiles discriminate sensitizing and irritating compounds. Toxicol Sci. 2010 Sep;117(1):81-9.
8 RNA-sequencing reveals long-term effects of silver nanoparticles on human lung cells. Sci Rep. 2018 Apr 27;8(1):6668.
9 Exposure to naphthalene induces naphthyl-keratin adducts in human epidermis in vitro and in vivo. Biomarkers. 2010 Sep;15(6):488-97.
10 ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.
11 Toxicity of xanthene food dyes by inhibition of human drug-metabolizing enzymes in a noncompetitive manner. J Environ Public Health. 2009;2009:953952.
12 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.
13 Proteasome inhibitors MG-132 and bortezomib induce AKR1C1, AKR1C3, AKR1B1, and AKR1B10 in human colon cancer cell lines SW-480 and HT-29. Chem Biol Interact. 2011 May 30;191(1-3):239-49.
14 Analysis of the in vitro synergistic effect of 5-fluorouracil and cisplatin on cervical carcinoma cells. Int J Gynecol Cancer. 2006 May-Jun;16(3):1321-9.
15 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.
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 Structural analysis of sulindac as an inhibitor of aldose reductase and AKR1B10. Chem Biol Interact. 2015 Jun 5;234:290-6.
18 In vitro evaluation of oxidative damage from organic solvent vapours on human skin. Toxicol In Vitro. 2006 Apr;20(3):324-31.
19 Antiinflammatory and aldose reductase inhibitory activity of some tricyclic arylacetic acids. J Med Chem. 1986 Nov;29(11):2347-51.
20 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
21 Design, synthesis and evaluation of caffeic acid phenethyl ester-based inhibitors targeting a selectivity pocket in the active site of human aldo-keto reductase 1B10. Eur J Med Chem. 2012 Feb;48:321-9.
22 Inhibition of 3(17)alpha-hydroxysteroid dehydrogenase (AKR1C21) by aldose reductase inhibitors. Bioorg Med Chem. 2008 Mar 15;16(6):3245-54.
23 CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
24 Novel, Potent Aldose Reductase Inhibitors: 3,4-dihydro-4-oxo-3-[[5-(trifluoromethyl)-2-benzothiazolyl] methyl]-1-phthalazineacetic Acid (Zopolrestat) and Congeners. J Med Chem. 1991 Jan;34(1):108-22.

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