Details of Xenobiotics-DME Interaction (XEOTIC)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0204)
DME Name Steroid 5-alpha-reductase 1 (SRD5A1), Homo sapiens DME Info
UniProt ID
S5A1_HUMAN
EC Number    EC: 1.3.1.22     (Click to Show/Hide the Complete EC Tree)
Oxidoreductase
CH-CH donor oxidoreductase
NAD/NADP acceptor oxidoreductase
EC: 1.3.1.22
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
                              Cadmium Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01503   XEOTIC Info Gene Form mRNA
                                 Classification Acute Toxic Substance
                                 DME Modulation Cadmium up-regulates the expression of DME SRD5A1 [1]
                  Environmental Pollutant Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              2,3-dibromopropyl-2,4,6-tribromophenyl ether Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01112   XEOTIC Info Gene Form mRNA
                                 Classification Environmental Pollutant
                                 DME Modulation 2,3-dibromopropyl-2,4,6-tribromophenyl ether inhibits the expression of DME SRD5A1 [2]
      Natural Product(s), Extract(s) or Medicine(s)
                  Plant Extract Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Plant extracts Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01574   XEOTIC Info Gene Form mRNA
                                 Classification Plant Extract
                                 DME Modulation Plant extracts inhibits the expression of DME SRD5A1 [3]
      Pharmaceutical Agent(s)
                  Approved/Marketed Drug Click to Show/Hide the Full List of Xenobiotics:        7 Xenobiotics
                              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 SRD5A1 [4]
                              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 SRD5A1 [5]
                              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 SRD5A1 [6]
                              Dutasteride Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00192   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Dutasteride inhibits the drug-metabolizing activity of DME SRD5A1 [7]
                              Dydrogesterone Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00403   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Dydrogesterone inhibits the expression of DME SRD5A1 [8]
                              Finasteride Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00129   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Finasteride inhibits the drug-metabolizing activity of DME SRD5A1 in Human prostate cancer cell lines (LNCaP) (IC50 = 0.0198 microM) [9]
                              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 SRD5A1 [10]
                  Drug in Phase 2 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Hydroxytamoxifen Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00634   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 2
                                 DME Modulation Hydroxytamoxifen up-regulates the expression of DME SRD5A1 [11]
                  Drug in Phase 1 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Dihydrotestosterone Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00536   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 1
                                 DME Modulation Dihydrotestosterone up-regulates the expression of DME SRD5A1 [2], [12]
                  Preclinical/Patented Drug Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              (+)-JQ1 Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00723   XEOTIC Info Gene Form mRNA
                                 Classification Drug in Preclinical Study
                                 DME Modulation (+)-JQ1 up-regulates the expression of DME SRD5A1 [13]
References
1 Using expression profiling to understand the effects of chronic cadmium exposure on MCF-7 breast cancer cells. PLoS One. 2013 Dec 20;8(12):e84646.
2 Identification of a group of brominated flame retardants as novel androgen receptor antagonists and potential neuronal and endocrine disrupters. Environ Int. 2015 Jan;74:60-70.
3 Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
4 Arsenic trioxide and cisplatin synergism increase cytotoxicity in human ovarian cancer cells: therapeutic potential for ovarian cancer. Cancer Sci. 2009 Dec;100(12):2459-64.
5 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
6 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.
7 Dutasteride affects progesterone metabolizing enzyme activity/expression in human breast cell lines resulting in suppression of cell proliferation and detachment. J Steroid Biochem Mol Biol. 2006 Aug;100(4-5):129-40.
8 Progestin effects on expression of AKR1C1-AKR1C3, SRD5A1 and PGR in the Z-12 endometriotic epithelial cell line. Chem Biol Interact. 2013 Feb 25;202(1-3):218-25.
9 A novel class of inhibitors for steroid 5alpha-reductase: synthesis and evaluation of umbelliferone derivatives. Bioorg Med Chem Lett. 2001 Sep 3;11(17):2361-3.
10 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.
11 Gene expression preferentially regulated by tamoxifen in breast cancer cells and correlations with clinical outcome. Cancer Res. 2006 Jul 15;66(14):7334-40.
12 Antiandrogenic mechanisms of pesticides in human LNCaP prostate and H295R adrenocortical carcinoma cells. Toxicol Sci. 2015 Jan;143(1):126-35.
13 Highly active combination of BRD4 antagonist and histone deacetylase inhibitor against human acute myelogenous leukemia cells. Mol Cancer Ther. 2014 May;13(5):1142-54.

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