Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3QER33)

• DOT Name: Ectonucleoside triphosphate diphosphohydrolase 7 (ENTPD7)
• Synonyms: NTPDase 7; EC 3.6.1.15; Lysosomal apyrase-like protein 1
• Gene Name: ENTPD7
• UniProt ID: ENTP7_HUMAN
• EC Number: 3.6.1.15
• Pfam ID: PF01150
• Sequence:
  MARISFSYLCPASWYFTVPTVSPFLRQRVAFLGLFFISCLLLLMLIIDFRHWSASLPRDR
  QYERYLARVGELEATDTEDPNLNYGLVVDCGSSGSRIFVYFWPRHNGNPHDLLDIKQMRD
  RNSQPVVKKIKPGISAMADTPEHASDYLRPLLSFAAAHVPVKKHKETPLYILCTAGMRLL
  PERKQLAILADLVKDLPLEFDFLFSQSQAEVISGKQEGVYAWIGINFVLGRFDHEDESDA
  EATQELAAGRRRTVGILDMGGASLQIAYEVPTSTSVLPAKQEEAAKILLAEFNLGCDVQH
  TEHVYRVYVTTFLGFGGNFARQRYEDLVLNETLNKNRLLGQKTGLSPDNPFLDPCLPVGL
  TDVVERNSQVLHVRGRGDWVSCGAMLSPLLARSNTSQASLNGIYQSPIDFNNSEFYGFSE
  FFYCTEDVLRIGGRYHGPTFAKAAQDYCGMAWSVLTQRFKNGLFSSHADEHRLKYQCFKS
  AWMYQVLHEGFHFPYDYPNLRTAQLVYDREVQWTLGAILYKTRFLPLRDLRQEGVRQAHG
  SWFRLSFVYNHYLFFACILVVLLAIFLYLLRLRRIHHRQTRASAPLDLLWLEEVVPMMGV
  QVGP
• Function: Catalyzes the hydrolysis of nucleoside triphosphates and diphosphates in a calcium- or magnesium-dependent manner. Preferentially hydrolyzes nucleoside 5'-triphosphates, with substrate preference for UTP > GTP > CTP. Hydrolyzes ATP and nucleoside diphosphates only to a minor extent.
• Reactome Pathway: Phosphate bond hydrolysis by NTPDase proteins (R-HSA-8850843)

Molecular Interaction Atlas (MIA) of This DOT

2 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 Ectonucleoside triphosphate diphosphohydrolase 7 (ENTPD7).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Ectonucleoside triphosphate diphosphohydrolase 7 (ENTPD7).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ectonucleoside triphosphate diphosphohydrolase 7 (ENTPD7).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ectonucleoside triphosphate diphosphohydrolase 7 (ENTPD7).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ectonucleoside triphosphate diphosphohydrolase 7 (ENTPD7).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ectonucleoside triphosphate diphosphohydrolase 7 (ENTPD7).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Ectonucleoside triphosphate diphosphohydrolase 7 (ENTPD7).	[6]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Ectonucleoside triphosphate diphosphohydrolase 7 (ENTPD7).	[7]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Ectonucleoside triphosphate diphosphohydrolase 7 (ENTPD7).	[8]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Ectonucleoside triphosphate diphosphohydrolase 7 (ENTPD7).	[6]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Ectonucleoside triphosphate diphosphohydrolase 7 (ENTPD7).	[8]
Fenofibrate	DMFKXDY	Approved	Fenofibrate decreases the expression of Ectonucleoside triphosphate diphosphohydrolase 7 (ENTPD7).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Ectonucleoside triphosphate diphosphohydrolase 7 (ENTPD7).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Ectonucleoside triphosphate diphosphohydrolase 7 (ENTPD7).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ectonucleoside triphosphate diphosphohydrolase 7 (ENTPD7).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Ectonucleoside triphosphate diphosphohydrolase 7 (ENTPD7).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Ectonucleoside triphosphate diphosphohydrolase 7 (ENTPD7).	[14]

References

• [1] 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.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
• [7] Methotrexate modulates folate phenotype and inflammatory profile in EA.hy 926 cells. Eur J Pharmacol. 2014 Jun 5;732:60-7.
• [8] 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.
• [9] 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.
• [10] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [11] 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.
• [12] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [13] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.