Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT03IQA5)

• DOT Name: 8-oxo-dGDP phosphatase NUDT18 (NUDT18)
• Synonyms: EC 3.6.1.58; 2-hydroxy-dADP phosphatase; 7,8-dihydro-8-oxoguanine phosphatase; MutT homolog 3; Nucleoside diphosphate-linked moiety X motif 18; Nudix motif 18
• Gene Name: NUDT18
• Related Disease:
  Breast adenocarcinoma
  Triple negative breast cancer
• UniProt ID: NUD18_HUMAN
• PDB ID: 3GG6; 4HVY
• EC Number: 3.6.1.58
• Pfam ID: PF00293
• Sequence:
  MASEGLAGALASVLAGQGSSVHSCDSAPAGEPPAPVRLRKNVCYVVLAVFLSEQDEVLLI
  QEAKRECRGSWYLPAGRMEPGETIVEALQREVKEEAGLHCEPETLLSVEERGPSWVRFVF
  LARPTGGILKTSKEADAESLQAAWYPRTSLPTPLRAHDILHLVELAAQYRQQARHPLILP
  QELPCDLVCQRLVATFTSAQTVWVLVGTVGMPHLPVTACGLDPMEQRGGMKMAVLRLLQE
  CLTLHHLVVEIKGLLGLQHLGRDHSDGICLNVLVTVAFRSPGIQDEPPKVRGENFSWWKV
  MEEDLQSQLLQRLQGSSVVPVNR
• Function: Mediates the hydrolysis of oxidized nucleoside diphosphate derivatives. Hydrolyzes 8-oxo-7,8-dihydroguanine (8-oxo-Gua)-containing deoxyribo- and ribonucleoside diphosphates to the monophosphates. Hydrolyzes 8-oxo-dGDP and 8-oxo-GDP with the same efficiencies. Hydrolyzes also 8-OH-dADP and 2-OH-dADP. Exhibited no or minimal hydrolysis activity against 8-oxo-dGTP, 8-oxo-GTP, dGTP, GTP, dGDP and GDP. Probably removes oxidized guanine nucleotides from both the DNA and RNA precursor pools.
• BioCyc Pathway: MetaCyc:ENSG00000173566-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast adenocarcinoma	DISMPHJ0	Strong	Biomarker	[1]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of 8-oxo-dGDP phosphatase NUDT18 (NUDT18).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of 8-oxo-dGDP phosphatase NUDT18 (NUDT18).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of 8-oxo-dGDP phosphatase NUDT18 (NUDT18).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of 8-oxo-dGDP phosphatase NUDT18 (NUDT18).	[5]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of 8-oxo-dGDP phosphatase NUDT18 (NUDT18).	[5]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of 8-oxo-dGDP phosphatase NUDT18 (NUDT18).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of 8-oxo-dGDP phosphatase NUDT18 (NUDT18).	[3]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of 8-oxo-dGDP phosphatase NUDT18 (NUDT18).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of 8-oxo-dGDP phosphatase NUDT18 (NUDT18).	[8]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of 8-oxo-dGDP phosphatase NUDT18 (NUDT18).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of 8-oxo-dGDP phosphatase NUDT18 (NUDT18).	[10]

References

• [1] Effect of bis(hydroxymethyl) alkanoate curcuminoid derivative MTH-3 on cell cycle arrest, apoptotic and autophagic pathway in triple-negative breast adenocarcinoma MDA-MB-231 cells: An in vitro study.Int J Oncol. 2018 Jan;52(1):67-76. doi: 10.3892/ijo.2017.4204. Epub 2017 Nov 14.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [4] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [5] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [6] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [7] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] 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.