Details of Xenobiotics-DME Interaction (XEOTIC)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0198)
DME Name Aldo-keto reductase 1C4 (AKR1C4), Homo sapiens DME Info
UniProt ID
AK1C4_HUMAN
EC Number    EC: 1.1.1.357     (Click to Show/Hide the Complete EC Tree)
Oxidoreductase
CH-OH donor oxidoreductase
NAD/NADP oxidoreductase
EC: 1.1.1.357
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
                              Chloropicrin Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01247   XEOTIC Info Gene Form mRNA
                                 Classification Acute Toxic Substance
                                 DME Modulation Chloropicrin up-regulates the expression of DME AKR1C4 [1]
                  Carcinogen Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              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 AKR1C4 [2], [3]
                  Health Hazard/Toxicant Click to Show/Hide the Full List of Xenobiotics:        2 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 AKR1C4 [4]
                              Medazepam Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00881   XEOTIC Info Gene Form Protein
                                 Classification Health Hazard
                                 DME Modulation Medazepam inhibits the drug-metabolizing activity of DME AKR1C4 [5]
      Natural Product(s), Extract(s) or Medicine(s)
                  Natural Mixture Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Particulate matter Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00919   XEOTIC Info Gene Form Protein
                                 Classification Natural Mixture
                                 DME Modulation Particulate matter induces the drug-metabolizing activity of DME AKR1C4 [6], [7]
                  Natural Product Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Octyl gallate Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01408   XEOTIC Info Gene Form mRNA
                                 Classification Natural Product
                                 DME Modulation Octyl gallate inhibits the expression of DME AKR1C4 [8]
                  Traditional Medicine Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Jinfukang Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00760   XEOTIC Info Gene Form mRNA
                                 Classification Traditional Medicine
                                 DME Modulation Jinfukang up-regulates the expression of DME AKR1C4 [9]
      Pharmaceutical Agent(s)
                  Approved/Marketed Drug Click to Show/Hide the Full List of Xenobiotics:      13 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 AKR1C4 [10]
                              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 AKR1C4 [11]
                              Diazepam Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00024   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Diazepam inhibits the drug-metabolizing activity of DME AKR1C4 [12], [13]
                              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 AKR1C4 [11]
                              Indomethacin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00047   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Indomethacin inhibits the drug-metabolizing activity of DME AKR1C4 (IC50 = 54 microM) [14]
                              Meclofenamic acid Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00415   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Meclofenamic acid inhibits the drug-metabolizing activity of DME AKR1C4 (IC50 > 100 microM) [15], [16]
                              Benzbromarone Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00492   XEOTIC Info Gene Form Protein
                                 Classification Drug Marketed but not Approved by US FDA
                                 DME Modulation Benzbromarone inhibits the drug-metabolizing activity of DME AKR1C4 [12]
                              Cloxazolam Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01258   XEOTIC Info Gene Form Protein
                                 Classification Drug Marketed but not Approved by US FDA
                                 DME Modulation Cloxazolam inhibits the drug-metabolizing activity of DME AKR1C4 [12]
                              Flufenamic acid Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00470   XEOTIC Info Gene Form Protein
                                 Classification Drug Marketed but not Approved by US FDA
                                 DME Modulation Flufenamic acid inhibits the drug-metabolizing activity of DME AKR1C4 (IC50 > 100 microM) [15], [16]
                              Flunitrazepam Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00498   XEOTIC Info Gene Form Protein
                                 Classification Drug Marketed but not Approved by US FDA
                                 DME Modulation Flunitrazepam inhibits the drug-metabolizing activity of DME AKR1C4 [13]
                              Gamolenic acid Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00510   XEOTIC Info Gene Form mRNA
                                 Classification Drug Marketed but not Approved by US FDA
                                 DME Modulation Gamolenic acid up-regulates the expression of DME AKR1C4 [17]
                              Glycyrrhetinic acid Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01319   XEOTIC Info Gene Form Protein
                                 Classification Drug Marketed but not Approved by US FDA
                                 DME Modulation Glycyrrhetinic acid inhibits the drug-metabolizing activity of DME AKR1C4 [12]
                              Hexestrol Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00769   XEOTIC Info Gene Form Protein
                                 Classification Drug Marketed but not Approved by US FDA
                                 DME Modulation Hexestrol inhibits the drug-metabolizing activity of DME AKR1C4 [12]
                  Drug in Phase 1 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              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 AKR1C4 (IC50 = 2.3 microM) [14]
                              Sodium arsenite Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00632   XEOTIC Info Gene Form Protein
                                 Classification Highest Clinical Status: Phase 1
                                 DME Modulation Sodium arsenite inhibits the expression of DME AKR1C4 and leads to decreasing the drug-metabolizing activity of this enzyme [18]
                  Preclinical/Patented Drug Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              NSC-668394 Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01403   XEOTIC Info Gene Form Protein
                                 Classification Patented Pharmaceutical Agent
                                 DME Modulation NSC-668394 induces the drug-metabolizing activity of DME AKR1C4 [19], [20]
                  Drug Marketed but Withdrawn from Market Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Phenolphthalein Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00521   XEOTIC Info Gene Form mRNA
                                 Classification Drug Marketed but Withdrawn from Market
                                 DME Modulation Phenolphthalein inhibits the expression of DME AKR1C4 [21]
      Other Chemical Compound(s) or Element(s)
                  Chemical Compound Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              1,10-phenanthroline Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00766   XEOTIC Info Gene Form Protein
                                 Classification Chemical Compound
                                 DME Modulation 1,10-phenanthroline inhibits the drug-metabolizing activity of DME AKR1C4 [12]
References
1 Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
2 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.
3 Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma. Toxicology. 2016 Mar 28;350-352:31-9.
4 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.
5 Clinical effects of maxacalcitol on secondary hyperparathyroidism of uremic patients. Am J Kidney Dis. 2001 Oct;38(4 Suppl 1):S147-51.
6 SODs are involved in the regulation of ICAM-1 expression in human melanoma and endothelial cells. Cell Mol Biol (Noisy-le-grand). 1999 Nov;45(7):1053-63.
7 Age-dependent basal level and induction capacity of copper-zinc and manganese superoxide dismutase and other scavenging enzyme activities in leukocytes from young and elderly adults. Am J Pathol. 1993 Jul;143(1):312-20.
8 Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
9 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
10 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
11 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.
12 Selective and potent inhibitors of human 20alpha-hydroxysteroid dehydrogenase (AKR1C1) that metabolizes neurosteroids derived from progesterone. Chem Biol Interact. 2003 Feb 1;143-144:503-13.
13 Substrate specificity of human 3(20)alpha-hydroxysteroid dehydrogenase for neurosteroids and its inhibition by benzodiazepines. Biol Pharm Bull. 2002 Apr;25(4):441-5.
14 Selective inhibition of human type-5 17beta-hydroxysteroid dehydrogenase (AKR1C3) by baccharin, a component of Brazilian propolis. J Nat Prod. 2012 Apr 27;75(4):716-21.
15 3-(3,4-Dihydroisoquinolin-2(1H)-ylsulfonyl)benzoic Acids: Highly Potent and Selective Inhibitors of the Type 5 17-beta-hydroxysteroid Dehydrogenase AKR1C3 J Med Chem. 2012 Sep 13;55(17):7746-58.
16 Synthesis and structure-activity relationships for 1-(4-(piperidin-1-ylsulfonyl)phenyl)pyrrolidin-2-ones as novel non-carboxylate inhibitors of the aldo-keto reductase enzyme AKR1C3. Eur J Med Chem. 2013 Apr;62:738-44.
17 Antineoplastic effects of gamma linolenic Acid on hepatocellular carcinoma cell lines. J Clin Biochem Nutr. 2010 Jul;47(1):81-90.
18 Arsenite decreases CYP3A4 and RXRalpha in primary human hepatocytes. Drug Metab Dispos. 2005 Jul;33(7):993-1003.
19 Nimesulide and indomethacin induce apoptosis in head and neck cancer cells. J Oral Pathol Med. 2004 Nov;33(10):607-13.
20 Differential effects of selective cyclooxygenase-2 inhibitors in inhibiting proliferation and induction of apoptosis in oral squamous cell carcinoma. Oncol Rep. 2008 Feb;19(2):425-33.
21 Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. Environ Toxicol. 2017 Jan;32(1):176-187.

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