Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTRT6Z9)

• DOT Name: Cancer-related nucleoside-triphosphatase (NTPCR)
• Synonyms: NTPase; EC 3.6.1.15; Nucleoside triphosphate phosphohydrolase
• Gene Name: NTPCR
• Related Disease:
  Attention deficit hyperactivity disorder
  Zika virus infection
  Ebola virus infection
  Hepatitis C virus infection
• UniProt ID: NTPCR_HUMAN
• PDB ID: 2I3B
• EC Number: 3.6.1.15
• Pfam ID: PF03266
• Sequence:
  MARHVFLTGPPGVGKTTLIHKASEVLKSSGVPVDGFYTEEVRQGGRRIGFDVVTLSGTRG
  PLSRVGLEPPPGKRECRVGQYVVDLTSFEQLALPVLRNADCSSGPGQRVCVIDEIGKMEL
  FSQLFIQAVRQTLSTPGTIILGTIPVPKGKPLALVEEIRNRKDVKVFNVTKENRNHLLPD
  IVTCVQSSRK
• Function: Has nucleotide phosphatase activity towards ATP, GTP, CTP, TTP and UTP. Hydrolyzes nucleoside diphosphates with lower efficiency.
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Thiamine metabolism (hsa00730)
  Metabolic pathways (hsa01100)
  Nucleotide metabolism (hsa01232)
• BioCyc Pathway: MetaCyc:HS06064-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Biomarker	[1]
Zika virus infection	DISQUCTY	Strong	Biomarker	[2]
Ebola virus infection	DISJAVM1	Limited	Biomarker	[3]
Hepatitis C virus infection	DISQ0M8R	Limited	Biomarker	[4]

18 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 Cancer-related nucleoside-triphosphatase (NTPCR).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cancer-related nucleoside-triphosphatase (NTPCR).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cancer-related nucleoside-triphosphatase (NTPCR).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cancer-related nucleoside-triphosphatase (NTPCR).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cancer-related nucleoside-triphosphatase (NTPCR).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cancer-related nucleoside-triphosphatase (NTPCR).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Cancer-related nucleoside-triphosphatase (NTPCR).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Cancer-related nucleoside-triphosphatase (NTPCR).	[12]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Cancer-related nucleoside-triphosphatase (NTPCR).	[11]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Cancer-related nucleoside-triphosphatase (NTPCR).	[11]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of Cancer-related nucleoside-triphosphatase (NTPCR).	[11]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of Cancer-related nucleoside-triphosphatase (NTPCR).	[11]
Adefovir dipivoxil	DMMAWY1	Approved	Adefovir dipivoxil increases the expression of Cancer-related nucleoside-triphosphatase (NTPCR).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Cancer-related nucleoside-triphosphatase (NTPCR).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Cancer-related nucleoside-triphosphatase (NTPCR).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Cancer-related nucleoside-triphosphatase (NTPCR).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Cancer-related nucleoside-triphosphatase (NTPCR).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Cancer-related nucleoside-triphosphatase (NTPCR).	[17]

References

• [1] Vibrio cholerae FeoB contains a dual nucleotide-specific NTPase domain essential for ferrous iron uptake.Proc Natl Acad Sci U S A. 2019 Mar 5;116(10):4599-4604. doi: 10.1073/pnas.1817964116. Epub 2019 Feb 13.
• [2] Structure and flexibility of non-structural proteins 3 and -5 of Dengue- and Zika viruses in solution.Prog Biophys Mol Biol. 2019 May;143:67-77. doi: 10.1016/j.pbiomolbio.2018.08.008. Epub 2018 Aug 29.
• [3] Ebola virus VP35has novel NTPase and helicase-like activities.Nucleic Acids Res. 2019 Jun 20;47(11):5837-5851. doi: 10.1093/nar/gkz340.
• [4] Isolation of specific and high-affinity RNA aptamers against NS3 helicase domain of hepatitis C virus.RNA. 2004 Aug;10(8):1277-90. doi: 10.1261/rna.7100904. Epub 2004 Jul 9.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [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] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [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] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] 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.
• [15] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [16] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [17] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.