Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVSKPAN)

• DOT Name: Selenoprotein W (SELENOW)
• Synonyms: SelW
• Gene Name: SELENOW
• Related Disease:
  Breast cancer
  Breast carcinoma
  Epilepsy
  Plasma cell myeloma
  Temporal lobe epilepsy
  Advanced cancer
  Clear cell renal carcinoma
  Neoplasm
  Obesity
  Renal cell carcinoma
• UniProt ID: SELW_HUMAN
• Pfam ID: PF10262
• Sequence:
  MALAVRVVYCGAUGYKSKYLQLKKKLEDEFPGRLDICGEGTPQATGFFEVMVAGKLIHSK
  KKGDGYVDTESKFLKLVAAIKAALAQG
• Function: Plays a role as a glutathione (GSH)-dependent antioxidant. May be involved in a redox-related process. May play a role in the myopathies of selenium deficiency.
• Tissue Specificity: Ubiquitously expressed with highest levels in skeletal muscle and heart, moderate levels in brain, spinal cord, thyroid, spleen, prostate, ovary, small intestine and colon, and lowest levels in liver and lymph node.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[1]
Epilepsy	DISBB28L	Strong	Biomarker	[2]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[3]
Temporal lobe epilepsy	DISNOPXX	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	moderate	Altered Expression	[1]
Clear cell renal carcinoma	DISBXRFJ	moderate	Biomarker	[4]
Neoplasm	DISZKGEW	moderate	Biomarker	[4]
Obesity	DIS47Y1K	moderate	Biomarker	[5]
Renal cell carcinoma	DISQZ2X8	moderate	Biomarker	[4]

14 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Selenoprotein W (SELENOW).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Selenoprotein W (SELENOW).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Selenoprotein W (SELENOW).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Selenoprotein W (SELENOW).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Selenoprotein W (SELENOW).	[11]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Selenoprotein W (SELENOW).	[12]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Selenoprotein W (SELENOW).	[13]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Selenoprotein W (SELENOW).	[14]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of Selenoprotein W (SELENOW).	[15]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of Selenoprotein W (SELENOW).	[15]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Selenoprotein W (SELENOW).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Selenoprotein W (SELENOW).	[17]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Selenoprotein W (SELENOW).	[18]
Buthionine sulfoximine	DMJ46CB	Investigative	Buthionine sulfoximine decreases the expression of Selenoprotein W (SELENOW).	[12]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Selenoprotein W (SELENOW).	[9]

References

• [1] PIWI-interacting RNA-36712 restrains breast cancer progression and chemoresistance by interaction with SEPW1 pseudogene SEPW1P RNA.Mol Cancer. 2019 Jan 12;18(1):9. doi: 10.1186/s12943-019-0940-3.
• [2] Changes in the expression of selenoproteins in mesial temporal lobe epilepsy patients.Cell Mol Neurobiol. 2009 Dec;29(8):1223-31. doi: 10.1007/s10571-009-9418-y.
• [3] Gene expression profiling of bone marrow endothelial cells in patients with multiple myeloma.Clin Cancer Res. 2009 Sep 1;15(17):5369-78. doi: 10.1158/1078-0432.CCR-09-0040. Epub 2009 Aug 18.
• [4] Cyanidin Curtails Renal Cell Carcinoma Tumorigenesis.Cell Physiol Biochem. 2018;46(6):2517-2531. doi: 10.1159/000489658. Epub 2018 May 5.
• [5] Selenoprotein W deficiency does not affect oxidative stress and insulin sensitivity in the skeletal muscle of high-fat diet-fed obese mice.Am J Physiol Cell Physiol. 2019 Dec 1;317(6):C1172-C1182. doi: 10.1152/ajpcell.00064.2019. Epub 2019 Sep 11.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights CYP26 cytochrome metabolism in differential all-trans retinoic acid sensitivity. Blood. 2007 May 15;109(10):4450-60.
• [8] 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.
• [9] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [10] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [11] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [12] Selenoprotein W as molecular target of methylmercury in human neuronal cells is down-regulated by GSH depletion. Biochem Biophys Res Commun. 2005 May 20;330(4):1095-102. doi: 10.1016/j.bbrc.2005.03.080.
• [13] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [14] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [15] Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res. 2005 Dec 15;65(24):11676-88.
• [16] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [17] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [18] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.