Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEWQJ6B)

• DOT Name: Neuropeptide Y receptor type 2 (NPY2R)
• Synonyms: NPY2-R; NPY-Y2 receptor; Y2 receptor
• Gene Name: NPY2R
• UniProt ID: NPY2R_HUMAN
• PDB ID: 7X9B; 7YON; 7YOO
• Pfam ID: PF00001
• Sequence:
  MGPIGAEADENQTVEEMKVEQYGPQTTPRGELVPDPEPELIDSTKLIEVQVVLILAYCSI
  ILLGVIGNSLVIHVVIKFKSMRTVTNFFIANLAVADLLVNTLCLPFTLTYTLMGEWKMGP
  VLCHLVPYAQGLAVQVSTITLTVIALDRHRCIVYHLESKISKRISFLIIGLAWGISALLA
  SPLAIFREYSLIEIIPDFEIVACTEKWPGEEKSIYGTVYSLSSLLILYVLPLGIISFSYT
  RIWSKLKNHVSPGAANDHYHQRRQKTTKMLVCVVVVFAVSWLPLHAFQLAVDIDSQVLDL
  KEYKLIFTVFHIIAMCSTFANPLLYGWMNSNYRKAFLSAFRCEQRLDAIHSEVSVTFKAK
  KNLEVRKNSGPNDSFTEATNV
• Function: Receptor for neuropeptide Y and peptide YY. The rank order of affinity of this receptor for pancreatic polypeptides is PYY > NPY > PYY (3-36) > NPY (2-36) > [Ile-31, Gln-34] PP > [Leu-31, Pro-34] NPY > PP, [Pro-34] PYY and NPY free acid.
• Tissue Specificity: High levels in amygdala, corpus callosum, hippocampus and subthalamic nucleus. Also detectable in caudate nucleus, hypothalamus and substantia nigra.
• KEGG Pathway: Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Peptide ligand-binding receptors (R-HSA-375276)

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 Neuropeptide Y receptor type 2 (NPY2R).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Neuropeptide Y receptor type 2 (NPY2R).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Neuropeptide Y receptor type 2 (NPY2R).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Neuropeptide Y receptor type 2 (NPY2R).	[3]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Neuropeptide Y receptor type 2 (NPY2R).	[4]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Neuropeptide Y receptor type 2 (NPY2R).	[5]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Neuropeptide Y receptor type 2 (NPY2R).	[6]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Neuropeptide Y receptor type 2 (NPY2R).	[4]
Methamphetamine	DMPM4SK	Approved	Methamphetamine increases the expression of Neuropeptide Y receptor type 2 (NPY2R).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Neuropeptide Y receptor type 2 (NPY2R).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 affects the expression of Neuropeptide Y receptor type 2 (NPY2R).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Neuropeptide Y receptor type 2 (NPY2R).	[10]

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] 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] 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.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [7] Protective effect of neuropeptide Y2 receptor activation against methamphetamine-induced brain endothelial cell alterations. Toxicol Lett. 2020 Nov 1;334:53-59. doi: 10.1016/j.toxlet.2020.09.013. Epub 2020 Sep 18.
• [8] 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.
• [9] The Bromodomain Inhibitor JQ1 and the Histone Deacetylase Inhibitor Panobinostat Synergistically Reduce N-Myc Expression and Induce Anticancer Effects. Clin Cancer Res. 2016 May 15;22(10):2534-44. doi: 10.1158/1078-0432.CCR-15-1666. Epub 2016 Jan 5.
• [10] 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.