Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3SSJDP)

• DOT Name: Neuronal pentraxin-2 (NPTX2)
• Synonyms: NP2; Neuronal pentraxin II; NP-II
• Gene Name: NPTX2
• UniProt ID: NPTX2_HUMAN
• Pfam ID: PF00354
• Sequence:
  MLALLAASVALAVAAGAQDSPAPGSRFVCTALPPEAVHAGCPLPAMPMQGGAQSPEEELR
  AAVLQLRETVVQQKETLGAQREAIRELTGKLARCEGLAGGKARGAGATGKDTMGDLPRDP
  GHVVEQLSRSLQTLKDRLESLEHQLRANVSNAGLPGDFREVLQQRLGELERQLLRKVAEL
  EDEKSLLHNETSAHRQKTESTLNALLQRVTELERGNSAFKSPDAFKVSLPLRTNYLYGKI
  KKTLPELYAFTICLWLRSSASPGIGTPFSYAVPGQANEIVLIEWGNNPIELLINDKVAQL
  PLFVSDGKWHHICVTWTTRDGMWEAFQDGEKLGTGENLAPWHPIKPGGVLILGQEQDTVG
  GRFDATQAFVGELSQFNIWDRVLRAQEIVNIANCSTNMPGNIIPWVDNNVDVFGGASKWP
  VETCEERLLDL
• Function: Likely to play role in the modification of cellular properties that underlie long-term plasticity. Binds to agar matrix in a calcium-dependent manner.
• Tissue Specificity: Brain, pancreas, liver, heart and skeletal muscle. Highest levels are seen in the testis.

Molecular Interaction Atlas (MIA) of This DOT

14 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 Neuronal pentraxin-2 (NPTX2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Neuronal pentraxin-2 (NPTX2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Neuronal pentraxin-2 (NPTX2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Neuronal pentraxin-2 (NPTX2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Neuronal pentraxin-2 (NPTX2).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Neuronal pentraxin-2 (NPTX2).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Neuronal pentraxin-2 (NPTX2).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Neuronal pentraxin-2 (NPTX2).	[9]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Neuronal pentraxin-2 (NPTX2).	[6]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Neuronal pentraxin-2 (NPTX2).	[10]
Gefitinib	DM15F0X	Approved	Gefitinib decreases the expression of Neuronal pentraxin-2 (NPTX2).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Neuronal pentraxin-2 (NPTX2).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Neuronal pentraxin-2 (NPTX2).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Neuronal pentraxin-2 (NPTX2).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Neuronal pentraxin-2 (NPTX2).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Neuronal pentraxin-2 (NPTX2).	[12]

References

• [1] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [2] 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.
• [3] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [7] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [8] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [9] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [10] Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
• [11] Identification of genes linked to gefitinib treatment in prostate cancer cell lines with or without resistance to androgen: a clue to application of gefitinib to hormone-resistant prostate cancer. Oncol Rep. 2006 Jun;15(6):1453-60.
• [12] 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.
• [13] Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int J Cancer. 2015 May 1;136(9):2055-64.
• [14] 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.