Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB9GJ1V)

• DOT Name: Ectonucleoside triphosphate diphosphohydrolase 8 (ENTPD8)
• Synonyms: E-NTPDase 8; NTPDase 8; NTPDase8; EC 3.6.1.5
• Gene Name: ENTPD8
• Related Disease:
  Pancreatic cancer
  Asthma
• UniProt ID: ENTP8_HUMAN
• EC Number: 3.6.1.5
• Pfam ID: PF01150
• Sequence:
  MGLSRKEQVFLALLGASGVSGLTALILLLVEATSVLLPTDIKFGIVFDAGSSHTSLFLYQ
  WLANKENGTGVVSQALACQVEGPGISSYTSNAAQAGESLQGCLEEALVLIPEAQHRKTPT
  FLGATAGMRLLSRKNSSQARDIFAAVTQVLGRSPVDFWGAELLAGQAEGAFGWITVNYGL
  GTLVKYSFTGEWIQPPEEMLVGALDMGGASTQITFVPGGPILDKSTQADFRLYGSDYSVY
  THSYLCFGRDQMLSRLLVGLVQSRPAALLRHPCYLSGYQTTLALGPLYESPCVHATPPLS
  LPQNLTVEGTGNPGACVSAIRELFNFSSCQGQEDCAFDGVYQPPLRGQFYAFSNFYYTFH
  FLNLTSRQPLSTVNATIWEFCQRPWKLVEASYPGQDRWLRDYCASGLYILTLLHEGYGFS
  EETWPSLEFRKQAGGVDIGWTLGYMLNLTGMIPADAPAQWRAESYGVWVAKVVFMVLALV
  AVVGAALVQLFWLQD
• Function: Canalicular ectonucleoside NTPDase responsible for the main hepatic NTPDase activity. Ectonucleoside NTPDases catalyze the hydrolysis of gamma- and beta-phosphate residues of nucleotides, playing a central role in concentration of extracellular nucleotides. Has activity toward ATP, ADP, UTP and UDP, but not toward AMP.
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Pyrimidine metabolism (hsa00240)
  Metabolic pathways (hsa01100)
  Nucleotide metabolism (hsa01232)
  Epstein-Barr virus infection (hsa05169)
• Reactome Pathway: Phosphate bond hydrolysis by NTPDase proteins (R-HSA-8850843)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Pancreatic cancer	DISJC981	moderate	Biomarker	[1]
Asthma	DISW9QNS	Limited	Altered Expression	[2]

4 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 Ectonucleoside triphosphate diphosphohydrolase 8 (ENTPD8).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Ectonucleoside triphosphate diphosphohydrolase 8 (ENTPD8).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Ectonucleoside triphosphate diphosphohydrolase 8 (ENTPD8).	[7]
Glyphosate	DM0AFY7	Investigative	Glyphosate affects the methylation of Ectonucleoside triphosphate diphosphohydrolase 8 (ENTPD8).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Ectonucleoside triphosphate diphosphohydrolase 8 (ENTPD8).	[4]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Ectonucleoside triphosphate diphosphohydrolase 8 (ENTPD8).	[4]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Ectonucleoside triphosphate diphosphohydrolase 8 (ENTPD8).	[5]

References

• [1] Identification of ENTPD8 and cytidine in pancreatic cancer by metabolomic and transcriptomic conjoint analysis.Cancer Sci. 2018 Sep;109(9):2811-2821. doi: 10.1111/cas.13733. Epub 2018 Sep 3.
• [2] Decreased expression of ectonucleotidase E-NPP1 in leukocytes from subjects with severe asthma exacerbation.Allergy. 2016 Jan;71(1):124-8. doi: 10.1111/all.12772. Epub 2015 Oct 20.
• [3] 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.
• [4] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [5] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [6] 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.
• [7] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [8] Association of Glyphosate Exposure with Blood DNA Methylation in a Cross-Sectional Study of Postmenopausal Women. Environ Health Perspect. 2022 Apr;130(4):47001. doi: 10.1289/EHP10174. Epub 2022 Apr 4.