Details of Xenobiotics-DME Interaction (XEOTIC)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0195)
DME Name Phosphodiesterase 5A (PDE5A), Homo sapiens DME Info
UniProt ID
PDE5A_HUMAN
EC Number    EC: 3.1.4.35     (Click to Show/Hide the Complete EC Tree)
Hydrolases
Ester bond hydrolase
Phosphoric diester hydrolase
EC: 3.1.4.35
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
                              KMUP 1 Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01356   XEOTIC Info Gene Form Protein
                                 Classification Acute Toxic Substance
                                 DME Modulation KMUP 1 inhibits the drug-metabolizing activity of DME PDE5A [1]
                  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 PDE5A [2]
                  Health Hazard/Toxicant Click to Show/Hide the Full List of Xenobiotics:        1 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 PDE5A [3]
      Natural Product(s), Extract(s) or Medicine(s)
                  Natural Product Click to Show/Hide the Full List of Xenobiotics:        4 Xenobiotics
                              Anthocyanins Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01522   XEOTIC Info Gene Form Protein
                                 Classification Natural Product
                                 DME Modulation Anthocyanins inhibits the drug-metabolizing activity of DME PDE5A [4]
                              Malvidin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01561   XEOTIC Info Gene Form Protein
                                 Classification Natural Product
                                 DME Modulation Malvidin inhibits the drug-metabolizing activity of DME PDE5A [5]
                              Malvidin-3-glucoside Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01562   XEOTIC Info Gene Form Protein
                                 Classification Natural Product
                                 DME Modulation Malvidin-3-glucoside inhibits the drug-metabolizing activity of DME PDE5A [6], [5]
                              Polydatin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01577   XEOTIC Info Gene Form Protein
                                 Classification Natural Product
                                 DME Modulation Polydatin inhibits the drug-metabolizing activity of DME PDE5A [7]
                  Traditional Medicine Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Jinfukang Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00760   XEOTIC Info Gene Form mRNA
                                 Classification Traditional Medicine
                                 DME Modulation Jinfukang inhibits the expression of DME PDE5A [8]
      Pharmaceutical Agent(s)
                  Approved/Marketed Drug Click to Show/Hide the Full List of Xenobiotics:      14 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 PDE5A [9]
                              Avobenzone Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00411   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Avobenzone up-regulates the expression of DME PDE5A [10]
                              Cisplatin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00334   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Cisplatin inhibits the expression of DME PDE5A [8]
                              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 PDE5A [11]
                              Dipyridamole Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00214   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Dipyridamole inhibits the drug-metabolizing activity of DME PDE5A (IC50 = 0.52 microM) [12]
                              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 PDE5A [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 PDE5A [14]
                              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 PDE5A [15]
                              Sildenafil citrate Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00212   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Sildenafil citrate inhibits the drug-metabolizing activity of DME PDE5A (IC50 = 0.0022 microM) [16]
                              Tadalafil Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00149   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Tadalafil inhibits the drug-metabolizing activity of DME PDE5A (IC50 = 0.0012 microM) [17]
                              Tretinoin Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00253   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Tretinoin up-regulates the expression of DME PDE5A [18]
                              Valproic acid Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00029   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Valproic acid inhibits the expression of DME PDE5A [19]
                              Vardenafil dihydrochloride Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00427   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Vardenafil dihydrochloride inhibits the expression of DME PDE5A [20]
                              Zoledronic acid Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00140   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Zoledronic acid inhibits the expression of DME PDE5A [21]
                  Drug in Phase 3 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        3 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 PDE5A [22], [23]
                              Icariin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00654   XEOTIC Info Gene Form Protein
                                 Classification Highest Clinical Status: Phase 3
                                 DME Modulation Icariin inhibits the drug-metabolizing activity of DME PDE5A in Monkey kidney tissue Fibroblast-like cell lines (COS)7 (IC50 = 5.9 microM) [24]
                              Resveratrol Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00568   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 3
                                 DME Modulation Resveratrol inhibits the expression of DME PDE5A [25]
                  Drug in Phase 2 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        2 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 PDE5A [26]
                              CP-461 Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01082   XEOTIC Info Gene Form Protein
                                 Classification Highest Clinical Status: Phase 2
                                 DME Modulation CP-461 inhibits the drug-metabolizing activity of DME PDE5A [27]
                  Drug in Phase 1 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Sodium arsenite Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00632   XEOTIC Info Gene Form Protein
                                 Classification Highest Clinical Status: Phase 1
                                 DME Modulation Sodium arsenite induces the drug-metabolizing activity of DME PDE5A [28]
                  Preclinical/Patented Drug Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              MY-5445 Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01383   XEOTIC Info Gene Form Protein
                                 Classification Patented Pharmaceutical Agent
                                 DME Modulation MY-5445 inhibits the drug-metabolizing activity of DME PDE5A (IC50 = 0.5 microM) [29]
                  Investigative Agent Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              3,7-bis(2-hydroxyethyl)icaritin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01136   XEOTIC Info Gene Form Protein
                                 Classification Investigative Agent
                                 DME Modulation 3,7-bis(2-hydroxyethyl)icaritin inhibits the drug-metabolizing activity of DME PDE5A in Monkey kidney tissue Fibroblast-like cell lines (COS)7 (IC50 = 0.074 microM) [24]
                              Phenylmercuric acetate Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00818   XEOTIC Info Gene Form mRNA
                                 Classification Investigative Agent
                                 DME Modulation Phenylmercuric acetate inhibits the expression of DME PDE5A [30]
      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 PDE5A [21]
References
1 KMUP-1 attenuates serum deprivation-induced neurotoxicity in SH-SY5Y cells: roles of PKG, PI3K/Akt and Bcl-2/Bax pathways. Toxicology. 2010 Jan 31;268(1-2):46-54.
2 Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
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 In vitro inhibition of human cGMP-specific phosphodiesterase-5 by polyphenols from red grapes. J Agric Food Chem. 2005 Mar 23;53(6):1960-5.
5 The inhibition of major human hepatic cytochrome P450 enzymes by 18 pesticides: comparison of the N-in-one and single substrate approaches. Toxicol In Vitro. 2013 Aug;27(5):1584-8.
6 An evaluation of the cytochrome P450 inhibition potential of selected pesticides in human hepatic microsomes. J Environ Sci Health B. 2009 Aug;44(6):553-63.
7 Pomegranate polyphenolics suppressed azoxymethane-induced colorectal aberrant crypt foci and inflammation: possible role of miR-126/VCAM-1 and miR-126/PI3K/AKT/mTOR. Carcinogenesis. 2013 Dec;34(12):2814-22.
8 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
9 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
10 A long-wave UVA filter avobenzone induces obesogenic phenotypes in normal human epidermal keratinocytes and mesenchymal stem cells. Arch Toxicol. 2019 Jul;93(7):1903-1915.
11 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.
12 Cyclic GMP phosphodiesterase inhibitors1The discovery of a novel potent inhibitor, 4-((3,4-(methylenedioxy)benzyl)amino)-6,7,8-trimethoxyquinazoline. J Med Chem. 1993 Nov 26;36(24):3765-70.
13 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.
14 Comparative effects of raloxifene, tamoxifen and estradiol on human osteoblasts in vitro: estrogen receptor dependent or independent pathways of raloxifene. J Steroid Biochem Mol Biol. 2009 Feb;113(3-5):281-9.
15 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.
16 4-(3-Chloro-4-methoxybenzyl)aminophthalazines: synthesis and inhibitory activity toward phosphodiesterase 5. J Med Chem. 2000 Jun 29;43(13):2523-9.
17 Synthesis of quinoline derivatives: discovery of a potent and selective phosphodiesterase 5 inhibitor for the treatment of Alzheimer's disease. Eur J Med Chem. 2013 Feb;60:285-94.
18 Omeprazole inhibits pancreatic cancer cell invasion through a nongenomic aryl hydrocarbon receptor pathway. Chem Res Toxicol. 2015 May 18;28(5):907-18.
19 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
20 Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
21 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.
22 Size-dependent effects of nanoparticles on the activity of cytochrome P450 isoenzymes. Toxicol Appl Pharmacol. 2010 Feb 1;242(3):326-32.
23 CDK inhibitor enhances the sensitivity to 5-fluorouracil in colorectal cancer cells. Int J Oncol. 2008 May;32(5):1105-10.
24 Potent inhibition of human phosphodiesterase-5 by icariin derivatives. J Nat Prod. 2008 Sep;71(9):1513-7.
25 Suppression by flavonoids of cyclooxygenase-2 promoter-dependent transcriptional activity in colon cancer cells: structure-activity relationship. Jpn J Cancer Res. 2000 Jul;91(7):686-91.
26 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.
27 Cyclic GMP-dependent protein kinase activation and induction by exisulind and CP461 in colon tumor cells. J Pharmacol Exp Ther. 2001 Nov;299(2):583-92.
28 Arsenite and its metabolites, MMA(III) and DMA(III), modify CYP3A4, PXR and RXR alpha expression in the small intestine of CYP3A4 transgenic mice. Toxicol Appl Pharmacol. 2009 Sep 1;239(2):162-8.
29 Inhibition of cyclic nucleotide phosphodiesterase by derivatives of 1,3-bis(cyclopropylmethyl)xanthine. J Med Chem. 1994 Feb 18;37(4):476-85.
30 Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.

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