Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTME0ZW5)

• DOT Name: Endonuclease domain-containing 1 protein (ENDOD1)
• Synonyms: EC 3.1.30.-
• Gene Name: ENDOD1
• Related Disease:
  Matthew-Wood syndrome
  Neoplasm
• UniProt ID: ENDD1_HUMAN
• EC Number: 3.1.30.-
• Pfam ID: PF01223
• Sequence:
  MGTARWLALGSLFALAGLLEGRLVGEEEAGFGECDKFFYAGTPPAGLAADSHVKICQRAE
  GAERFATLYSTRDRIPVYSAFRAPRPAPGGAEQRWLVEPQIDDPNSNLEEAINEAEAITS
  VNSLGSKQALNTDYLDSDYQRGQLYPFSLSSDVQVATFTLTNSAPMTQSFQERWYVNLHS
  LMDRALTPQCGSGEDLYILTGTVPSDYRVKDKVAVPEFVWLAACCAVPGGGWAMGFVKHT
  RDSDIIEDVMVKDLQKLLPFNPQLFQNNCGETEQDTEKMKKILEVVNQIQDEERMVQSQK
  SSSPLSSTRSKRSTLLPPEASEGSSSFLGKLMGFIATPFIKLFQLIYYLVVAILKNIVYF
  LWCVTKQVINGIESCLYRLGSATISYFMAIGEELVSIPWKVLKVVAKVIRALLRILCCLL
  KAICRVLSIPVRVLVDVATFPVYTMGAIPIVCKDIALGLGGTVSLLFDTAFGTLGGLFQV
  VFSVCKRIGYKVTFDNSGEL
• Function: May act as a DNase and a RNase. Plays a role in the modulation of innate immune signaling through the cGAS-STING pathway by interacting with RNF26.
• Reactome Pathway: Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Matthew-Wood syndrome	DISA7HR7	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]

22 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 Endonuclease domain-containing 1 protein (ENDOD1).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Endonuclease domain-containing 1 protein (ENDOD1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Endonuclease domain-containing 1 protein (ENDOD1).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Endonuclease domain-containing 1 protein (ENDOD1).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Endonuclease domain-containing 1 protein (ENDOD1).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Endonuclease domain-containing 1 protein (ENDOD1).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Endonuclease domain-containing 1 protein (ENDOD1).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Endonuclease domain-containing 1 protein (ENDOD1).	[10]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Endonuclease domain-containing 1 protein (ENDOD1).	[11]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Endonuclease domain-containing 1 protein (ENDOD1).	[12]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Endonuclease domain-containing 1 protein (ENDOD1).	[13]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Endonuclease domain-containing 1 protein (ENDOD1).	[14]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Endonuclease domain-containing 1 protein (ENDOD1).	[15]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Endonuclease domain-containing 1 protein (ENDOD1).	[16]
Isoflavone	DM7U58J	Phase 4	Isoflavone decreases the expression of Endonuclease domain-containing 1 protein (ENDOD1).	[17]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Endonuclease domain-containing 1 protein (ENDOD1).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Endonuclease domain-containing 1 protein (ENDOD1).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Endonuclease domain-containing 1 protein (ENDOD1).	[20]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Endonuclease domain-containing 1 protein (ENDOD1).	[22]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Endonuclease domain-containing 1 protein (ENDOD1).	[23]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Endonuclease domain-containing 1 protein (ENDOD1).	[24]
Bilirubin	DMI0V4O	Investigative	Bilirubin decreases the expression of Endonuclease domain-containing 1 protein (ENDOD1).	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Endonuclease domain-containing 1 protein (ENDOD1).	[21]

References

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• [10] 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.
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• [12] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [13] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [14] Gene expression profile of human lymphoid CEM cells sensitive and resistant to glucocorticoid-evoked apoptosis. Genomics. 2003 Jun;81(6):543-55.
• [15] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [16] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [17] Soy isoflavones exert differential effects on androgen responsive genes in LNCaP human prostate cancer cells. J Nutr. 2007 Apr;137(4):964-72.
• [18] 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.
• [19] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [20] 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.
• [21] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
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• [24] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [25] Global changes in gene regulation demonstrate that unconjugated bilirubin is able to upregulate and activate select components of the endoplasmic reticulum stress response pathway. J Biochem Mol Toxicol. 2010 Mar-Apr;24(2):73-88.