Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNI9MFH)

• DOT Name: 5'-nucleotidase domain-containing protein 1 (NT5DC1)
• Synonyms: EC 3.1.3.-
• Gene Name: NT5DC1
• Related Disease:
  Age-related macular degeneration
  Narcolepsy
  Chronic obstructive pulmonary disease
  Melanoma
  Myopia
• UniProt ID: NT5D1_HUMAN
• EC Number: 3.1.3.-
• Pfam ID: PF05761
• Sequence:
  MAQHFSLAACDVVGFDLDHTLCRYNLPESAPLIYNSFAQFLVKEKGYDKELLNVTPEDWD
  FCCKGLALDLEDGNFLKLANNGTVLRASHGTKMMTPEVLAEAYGKKEWKHFLSDTGMACR
  SGKYYFYDNYFDLPGALLCARVVDYLTKLNNGQKTFDFWKDIVAAIQHNYKMSAFKENCG
  IYFPEIKRDPGRYLHSCPESVKKWLRQLKNAGKILLLITSSHSDYCRLLCEYILGNDFTD
  LFDIVITNALKPGFFSHLPSQRPFRTLENDEEQEALPSLDKPGWYSQGNAVHLYELLKKM
  TGKPEPKVVYFGDSMHSDIFPARHYSNWETVLILEELRGDEGTRSQRPEESEPLEKKGKY
  EGPKAKPLNTSSKKWGSFFIDSVLGLENTEDSLVYTWSCKRISTYSTIAIPSIEAIAELP
  LDYKFTRFSSSNSKTAGYYPNPPLVLSSDETLISK

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Age-related macular degeneration	DIS0XS2C	Strong	Genetic Variation	[1]
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[2]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Genetic Variation	[3]
Melanoma	DIS1RRCY	Limited	Biomarker	[4]
Myopia	DISK5S60	Limited	Genetic Variation	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of 5'-nucleotidase domain-containing protein 1 (NT5DC1).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of 5'-nucleotidase domain-containing protein 1 (NT5DC1).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of 5'-nucleotidase domain-containing protein 1 (NT5DC1).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of 5'-nucleotidase domain-containing protein 1 (NT5DC1).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of 5'-nucleotidase domain-containing protein 1 (NT5DC1).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of 5'-nucleotidase domain-containing protein 1 (NT5DC1).	[11]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of 5'-nucleotidase domain-containing protein 1 (NT5DC1).	[12]
Clorgyline	DMCEUJD	Approved	Clorgyline increases the expression of 5'-nucleotidase domain-containing protein 1 (NT5DC1).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of 5'-nucleotidase domain-containing protein 1 (NT5DC1).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of 5'-nucleotidase domain-containing protein 1 (NT5DC1).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of 5'-nucleotidase domain-containing protein 1 (NT5DC1).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of 5'-nucleotidase domain-containing protein 1 (NT5DC1).	[18]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of 5'-nucleotidase domain-containing protein 1 (NT5DC1).	[14]

References

• [1] Seven new loci associated with age-related macular degeneration.Nat Genet. 2013 Apr;45(4):433-9, 439e1-2. doi: 10.1038/ng.2578. Epub 2013 Mar 3.
• [2] Genome-wide association database developed in the Japanese Integrated Database Project.J Hum Genet. 2009 Sep;54(9):543-6. doi: 10.1038/jhg.2009.68. Epub 2009 Jul 24.
• [3] Single-nucleotide polymorphisms in the TSPYL-4 and NT5DC1 genes are associated with susceptibility to chronic obstructive pulmonary disease.Mol Med Rep. 2012 Sep;6(3):631-8. doi: 10.3892/mmr.2012.964. Epub 2012 Jun 25.
• [4] Aggressiveness of human melanoma xenograft models is promoted by aneuploidy-driven gene expression deregulation.Oncotarget. 2012 Apr;3(4):399-413. doi: 10.18632/oncotarget.473.
• [5] Detection and interpretation of shared genetic influences on 42 human traits.Nat Genet. 2016 Jul;48(7):709-17. doi: 10.1038/ng.3570. Epub 2016 May 16.
• [6] 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.
• [7] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [8] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [9] 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.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [12] 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.
• [13] Anti-oncogenic and pro-differentiation effects of clorgyline, a monoamine oxidase A inhibitor, on high grade prostate cancer cells. BMC Med Genomics. 2009 Aug 20;2:55. doi: 10.1186/1755-8794-2-55.
• [14] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [15] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [16] 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.
• [17] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [18] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.