Details of Drug Off-Target (DOT)

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

• DOT Name: 5'-nucleotidase domain-containing protein 2 (NT5DC2)
• Synonyms: EC 3.1.3.-
• Gene Name: NT5DC2
• Related Disease:
  Brain neoplasm
  Glioblastoma multiforme
  Glioma
  Knee osteoarthritis
  Schizophrenia
  Acute myelogenous leukaemia
• UniProt ID: NT5D2_HUMAN
• EC Number: 3.1.3.-
• Pfam ID: PF05761
• Sequence:
  MRVESGSAQERGILLESLSTLLEKTTASHEGRAPGNRELTDLLPPEVCSLLNPAAIYANN
  EISLRDVEVYGFDYDYTLAQYADALHPEIFSTARDILIEHYKYPEGIRKYDYNPSFAIRG
  LHYDIQKSLLMKIDAFHYVQLGTAYRGLQPVPDEEVIELYGGTQHIPLYQMSGFYGKGPS
  IKQFMDIFSLPEMALLSCVVDYFLGHSLEFDQAHLYKDVTDAIRDVHVKGLMYQWIEQDM
  EKYILRGDETFAVLSRLVAHGKQLFLITNSPFSFVDKGMRHMVGPDWRQLFDVVIVQADK
  PSFFTDRRKPFRKLDEKGSLQWDRITRLEKGKIYRQGNLFDFLRLTEWRGPRVLYFGDHL
  YSDLADLMLRHGWRTGAIIPELEREIRIINTEQYMHSLTWQQALTGLLERMQTYQDAESR
  QVLAAWMKERQELRCITKALFNAQFGSIFRTFHNPTYFSRRLVRFSDLYMASLSCLLNYR
  VDFTFYPRRTPLQHEAPLWMDQLCTGCMKTPFLGDMAHIR

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Brain neoplasm	DISY3EKS	Strong	Altered Expression	[1]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[1]
Glioma	DIS5RPEH	Strong	Biomarker	[1]
Knee osteoarthritis	DISLSNBJ	Strong	Genetic Variation	[2]
Schizophrenia	DISSRV2N	Strong	Biomarker	[3]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[4]

2 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 5'-nucleotidase domain-containing protein 2 (NT5DC2).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of 5'-nucleotidase domain-containing protein 2 (NT5DC2).	[15]

15 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 2 (NT5DC2).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of 5'-nucleotidase domain-containing protein 2 (NT5DC2).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of 5'-nucleotidase domain-containing protein 2 (NT5DC2).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of 5'-nucleotidase domain-containing protein 2 (NT5DC2).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of 5'-nucleotidase domain-containing protein 2 (NT5DC2).	[10]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of 5'-nucleotidase domain-containing protein 2 (NT5DC2).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of 5'-nucleotidase domain-containing protein 2 (NT5DC2).	[12]
Selenium	DM25CGV	Approved	Selenium increases the expression of 5'-nucleotidase domain-containing protein 2 (NT5DC2).	[13]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of 5'-nucleotidase domain-containing protein 2 (NT5DC2).	[14]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of 5'-nucleotidase domain-containing protein 2 (NT5DC2).	[13]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of 5'-nucleotidase domain-containing protein 2 (NT5DC2).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of 5'-nucleotidase domain-containing protein 2 (NT5DC2).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of 5'-nucleotidase domain-containing protein 2 (NT5DC2).	[18]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of 5'-nucleotidase domain-containing protein 2 (NT5DC2).	[19]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of 5'-nucleotidase domain-containing protein 2 (NT5DC2).	[20]

References

• [1] NT5DC2 promotes tumorigenicity of glioma stem-like cells by upregulating fyn.Cancer Lett. 2019 Jul 10;454:98-107. doi: 10.1016/j.canlet.2019.04.003. Epub 2019 Apr 10.
• [2] Genome-wide analyses using UK Biobank data provide insights into the genetic architecture of osteoarthritis.Nat Genet. 2018 Apr;50(4):549-558. doi: 10.1038/s41588-018-0079-y. Epub 2018 Mar 20.
• [3] Identification by nano-LC-MS/MS of NT5DC2 as a protein binding to tyrosine hydroxylase: Down-regulation of NT5DC2 by siRNA increases catecholamine synthesis in PC12D cells.Biochem Biophys Res Commun. 2019 Sep 3;516(4):1060-1065. doi: 10.1016/j.bbrc.2019.06.156. Epub 2019 Jul 3.
• [4] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [5] 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.
• [6] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [7] 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.
• [8] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [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] 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.
• [12] 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.
• [13] 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.
• [14] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [15] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [16] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [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] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [19] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [20] An in vitro strategy using multiple human induced pluripotent stem cell-derived models to assess the toxicity of chemicals: A case study on paraquat. Toxicol In Vitro. 2022 Jun;81:105333. doi: 10.1016/j.tiv.2022.105333. Epub 2022 Feb 16.