Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK75XGA)

• DOT Name: Neurotrophin-3 (NTF3)
• Synonyms: NT-3; HDNF; Nerve growth factor 2; NGF-2; Neurotrophic factor
• Gene Name: NTF3
• UniProt ID: NTF3_HUMAN
• PDB ID: 1B8K; 1BND; 1NT3; 3BUK
• Pfam ID: PF00243 ; PF19338
• Sequence:
  MSILFYVIFLAYLRGIQGNNMDQRSLPEDSLNSLIIKLIQADILKNKLSKQMVDVKENYQ
  STLPKAEAPREPERGGPAKSAFQPVIAMDTELLRQQRRYNSPRVLLSDSTPLEPPPLYLM
  EDYVGSPVVANRTSRRKRYAEHKSHRGEYSVCDSESLWVTDKSSAIDIRGHQVTVLGEIK
  TGNSPVKQYFYETRCKEARPVKNGCRGIDDKHWNSQCKTSQTYVRALTSENNKLVGWRWI
  RIDTSCVCALSRKIGRT
• Function: Seems to promote the survival of visceral and proprioceptive sensory neurons.
• Tissue Specificity: Brain and peripheral tissues.
• KEGG Pathway:
  MAPK sig.ling pathway (hsa04010)
  Ras sig.ling pathway (hsa04014)
  PI3K-Akt sig.ling pathway (hsa04151)
  Neurotrophin sig.ling pathway (hsa04722)
• Reactome Pathway:
  NTF3 activates NTRK3 signaling (R-HSA-9034013)
  Signaling by NTRK3 (TRKC) (R-HSA-9034015)
  Activated NTRK3 signals through PLCG1 (R-HSA-9034793)
  Activated NTRK3 signals through RAS (R-HSA-9034864)
  Activated NTRK3 signals through PI3K (R-HSA-9603381)
  NTF3 activates NTRK2 (TRKB) signaling (R-HSA-9025046)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Neurotrophin-3 (NTF3).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Neurotrophin-3 (NTF3).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Neurotrophin-3 (NTF3).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Neurotrophin-3 (NTF3).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Neurotrophin-3 (NTF3).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Neurotrophin-3 (NTF3).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Neurotrophin-3 (NTF3).	[4]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Neurotrophin-3 (NTF3).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Neurotrophin-3 (NTF3).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Neurotrophin-3 (NTF3).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Neurotrophin-3 (NTF3).	[7]

References

• [1] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [2] 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.
• [3] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [4] 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.
• [5] Prenatal arsenic exposure and shifts in the newborn proteome: interindividual differences in tumor necrosis factor (TNF)-responsive signaling. Toxicol Sci. 2014 Jun;139(2):328-37. doi: 10.1093/toxsci/kfu053. Epub 2014 Mar 27.
• [6] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [7] 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.
• [8] 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.
• [9] 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.