Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY807N5)

• DOT Name: Ectonucleotide pyrophosphatase/phosphodiesterase family member 5 (ENPP5)
• Synonyms: E-NPP 5; NPP-5; EC 3.1.-.-
• Gene Name: ENPP5
• Related Disease:
  Prostate cancer
  Prostate neoplasm
• UniProt ID: ENPP5_HUMAN
• PDB ID: 5VEM
• EC Number: 3.1.-.-
• Pfam ID: PF01663
• Sequence:
  MTSKFLLVSFILAALSLSTTFSLQPDQQKVLLVSFDGFRWDYLYKVPTPHFHYIMKYGVH
  VKQVTNVFITKTYPNHYTLVTGLFAENHGIVANDMFDPIRNKSFSLDHMNIYDSKFWEEA
  TPIWITNQRAGHTSGAAMWPGTDVKIHKRFPTHYMPYNESVSFEDRVAKIIEWFTSKEPI
  NLGLLYWEDPDDMGHHLGPDSPLMGPVISDIDKKLGYLIQMLKKAKLWNTLNLIITSDHG
  MTQCSEERLIELDQYLDKDHYTLIDQSPVAAILPKEGKFDEVYEALTHAHPNLTVYKKED
  VPERWHYKYNSRIQPIIAVADEGWHILQNKSDDFLLGNHGYDNALADMHPIFLAHGPAFR
  KNFSKEAMNSTDLYPLLCHLLNITAMPHNGSFWNVQDLLNSAMPRVVPYTQSTILLPGSV
  KPAEYDQEGSYPYFIGVSLGSIIVIVFFVIFIKHLIHSQIPALQDMHAEIAQPLLQA
• Function: Can hydrolyze NAD but cannot hydrolyze nucleotide di- and triphosphates. Lacks lysopholipase D activity. May play a role in neuronal cell communication.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Prostate cancer	DISF190Y	Strong	Biomarker	[1]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[1]

10 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 Ectonucleotide pyrophosphatase/phosphodiesterase family member 5 (ENPP5).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ectonucleotide pyrophosphatase/phosphodiesterase family member 5 (ENPP5).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ectonucleotide pyrophosphatase/phosphodiesterase family member 5 (ENPP5).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Ectonucleotide pyrophosphatase/phosphodiesterase family member 5 (ENPP5).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Ectonucleotide pyrophosphatase/phosphodiesterase family member 5 (ENPP5).	[6]
Cocaine	DMSOX7I	Approved	Cocaine increases the expression of Ectonucleotide pyrophosphatase/phosphodiesterase family member 5 (ENPP5).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Ectonucleotide pyrophosphatase/phosphodiesterase family member 5 (ENPP5).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Ectonucleotide pyrophosphatase/phosphodiesterase family member 5 (ENPP5).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Ectonucleotide pyrophosphatase/phosphodiesterase family member 5 (ENPP5).	[11]
biochanin A	DM0HPWY	Investigative	biochanin A decreases the expression of Ectonucleotide pyrophosphatase/phosphodiesterase family member 5 (ENPP5).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Ectonucleotide pyrophosphatase/phosphodiesterase family member 5 (ENPP5).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Ectonucleotide pyrophosphatase/phosphodiesterase family member 5 (ENPP5).	[9]

References

• [1] Identification of genes potentially involved in the acquisition of androgen-independent and metastatic tumor growth in an autochthonous genetically engineered mouse prostate cancer model.Prostate. 2007 Jan 1;67(1):83-106. doi: 10.1002/pros.20505.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [4] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [5] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [6] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [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] Gene expression profile of the nucleus accumbens of human cocaine abusers: evidence for dysregulation of myelin. J Neurochem. 2004 Mar;88(5):1211-9. doi: 10.1046/j.1471-4159.2003.02247.x.
• [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] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [11] 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.
• [12] Mechanisms of the growth inhibitory effects of the isoflavonoid biochanin A on LNCaP cells and xenografts. Prostate. 2002 Aug 1;52(3):201-12.