Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYCJ5H6)

• DOT Name: Protein DEK (DEK)
• Gene Name: DEK
• UniProt ID: DEK_HUMAN
• PDB ID: 1Q1V; 2JX3
• Pfam ID: PF08766
• Sequence:
  MSASAPAAEGEGTPTQPASEKEPEMPGPREESEEEEDEDDEEEEEEEKEKSLIVEGKREK
  KKVERLTMQVSSLQREPFTIAQGKGQKLCEIERIHFFLSKKKTDELRNLHKLLYNRPGTV
  SSLKKNVGQFSGFPFEKGSVQYKKKEEMLKKFRNAMLKSICEVLDLERSGVNSELVKRIL
  NFLMHPKPSGKPLPKSKKTCSKGSKKERNSSGMARKAKRTKCPEILSDESSSDEDEKKNK
  EESSDDEDKESEEEPPKKTAKREKPKQKATSKSKKSVKSANVKKADSSTTKKNQNSSKKE
  SESEDSSDDEPLIKKLKKPPTDEELKETIKKLLASANLEEVTMKQICKKVYENYPTYDLT
  ERKDFIKTTVKELIS
• Function: Involved in chromatin organization.
• Tissue Specificity: Ubiquitous. Expressed at relatively high levels.
• Reactome Pathway:
  Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors (R-HSA-8864260)
  Transcriptional regulation of granulopoiesis (R-HSA-9616222)
  B-WICH complex positively regulates rRNA expression (R-HSA-5250924)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Protein DEK (DEK) decreases the response to substance of Cisplatin.	[22]

This DOT Affected the Regulation of Drug Effects of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Ethanol	DMDRQZU	Approved	Protein DEK (DEK) increases the secretion of Ethanol.	[23]
Oxypurinol	DMURH4X	Phase 2/3	Protein DEK (DEK) increases the secretion of Oxypurinol.	[23]

This DOT Affected the Biotransformations of 6 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Glutathione	DMAHMT9	Approved	Protein DEK (DEK) decreases the chemical synthesis of Glutathione.	[23]
Creatine ALS-08	DMKD2BQ	Phase 3	Protein DEK (DEK) increases the chemical synthesis of Creatine ALS-08.	[23]
N1-methylnicotinamide	DM16PWF	Phase 2/3	Protein DEK (DEK) decreases the chemical synthesis of N1-methylnicotinamide.	[23]
Taurine	DMVW7N3	Investigative	Protein DEK (DEK) increases the chemical synthesis of Taurine.	[23]
Nicotinamide-Adenine-Dinucleotide	DM9LRKB	Investigative	Protein DEK (DEK) increases the oxidation of Nicotinamide-Adenine-Dinucleotide.	[23]
Formic Acid	DMNFZC6	Investigative	Protein DEK (DEK) decreases the chemical synthesis of Formic Acid.	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Protein DEK (DEK).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein DEK (DEK).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein DEK (DEK).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein DEK (DEK).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein DEK (DEK).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Protein DEK (DEK).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein DEK (DEK).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Protein DEK (DEK).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Protein DEK (DEK).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Protein DEK (DEK).	[10]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Protein DEK (DEK).	[10]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Protein DEK (DEK).	[6]
Folic acid	DMEMBJC	Approved	Folic acid affects the expression of Protein DEK (DEK).	[11]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Protein DEK (DEK).	[12]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Protein DEK (DEK).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein DEK (DEK).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Protein DEK (DEK).	[17]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Protein DEK (DEK).	[18]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Protein DEK (DEK).	[19]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Protein DEK (DEK).	[20]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Protein DEK (DEK).	[6]
CATECHIN	DMY38SB	Investigative	CATECHIN decreases the expression of Protein DEK (DEK).	[21]
propylpyrazoletriol	DMTCP8K	Investigative	propylpyrazoletriol increases the expression of Protein DEK (DEK).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Protein DEK (DEK).	[14]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Protein DEK (DEK).	[15]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Protein DEK (DEK).	[15]

References

• [1] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] 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.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] The DEK oncogene is a target of steroid hormone receptor signaling in breast cancer. PLoS One. 2012;7(10):e46985. doi: 10.1371/journal.pone.0046985. Epub 2012 Oct 10.
• [7] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [8] 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.
• [9] 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.
• [10] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [11] Folate deficiency in normal human fibroblasts leads to altered expression of genes primarily linked to cell signaling, the cytoskeleton and extracellular matrix. J Nutr Biochem. 2007 Aug;18(8):541-52. doi: 10.1016/j.jnutbio.2006.11.002. Epub 2007 Feb 22.
• [12] Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
• [13] Interactive gene expression pattern in prostate cancer cells exposed to phenolic antioxidants. Life Sci. 2002 Mar 1;70(15):1821-39.
• [14] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [15] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [16] 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.
• [17] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [18] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [19] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.
• [20] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.
• [21] Epicatechin and a cocoa polyphenolic extract modulate gene expression in human Caco-2 cells. J Nutr. 2004 Oct;134(10):2509-16.
• [22] Integrin 1, v, 6 effectors p130Cas, Src and talin regulate carcinoma invasion and chemoresistance. Biochem Biophys Res Commun. 2011 Mar 11;406(2):171-6. doi: 10.1016/j.bbrc.2011.01.109. Epub 2011 Feb 1.
• [23] Overexpression of the human DEK oncogene reprograms cellular metabolism and promotes glycolysis. PLoS One. 2017 May 30;12(5):e0177952. doi: 10.1371/journal.pone.0177952. eCollection 2017.