Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4ICV3P)

• DOT Name: Pro-neuropeptide Y (NPY)
• Gene Name: NPY
• UniProt ID: NPY_HUMAN
• PDB ID: 1QFA; 1RON; 7RTA; 7VGX; 7X9A; 7X9B; 7YOO
• Pfam ID: PF00159
• Sequence:
  MLGNKRLGLSGLTLALSLLVCLGALAEAYPSKPDNPGEDAPAEDMARYYSALRHYINLIT
  RQRYGKRSSPETLISDLLMRESTENVPRTRLEDPAMW
• Function: NPY is implicated in the control of feeding and in secretion of gonadotrophin-release hormone.
• Tissue Specificity: One of the most abundant peptides in the nervous system. Also found in some chromaffin cells of the adrenal medulla.
• KEGG Pathway:
  cAMP sig.ling pathway (hsa04024)
  Neuroactive ligand-receptor interaction (hsa04080)
  Adipocytokine sig.ling pathway (hsa04920)
  Regulation of lipolysis in adipocytes (hsa04923)
  Alcoholism (hsa05034)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes (R-HSA-9615017)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 5 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Mifepristone	DMGZQEF	Approved	Pro-neuropeptide Y (NPY) increases the Hyperphagia ADR of Mifepristone.	[15]
Adenosine triphosphate	DM79F6G	Approved	Pro-neuropeptide Y (NPY) affects the response to substance of Adenosine triphosphate.	[10]
Norepinephrine	DMOUC09	Approved	Pro-neuropeptide Y (NPY) affects the response to substance of Norepinephrine.	[10]
Reserpine	DM6VM38	Approved	Pro-neuropeptide Y (NPY) increases the Flushing ADR of Reserpine.	[15]
Topiramate	DM82Z30	Approved	Pro-neuropeptide Y (NPY) increases the Weight decreased ADR of Topiramate.	[15]

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 Pro-neuropeptide Y (NPY).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Pro-neuropeptide Y (NPY).	[2]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Pro-neuropeptide Y (NPY).	[3]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Pro-neuropeptide Y (NPY).	[4]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Pro-neuropeptide Y (NPY).	[5]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Pro-neuropeptide Y (NPY).	[6]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Pro-neuropeptide Y (NPY).	[4]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Pro-neuropeptide Y (NPY).	[7]
Hydrocortisone	DMGEMB7	Approved	Hydrocortisone affects the expression of Pro-neuropeptide Y (NPY).	[8]
Orlistat	DMRJSP8	Approved	Orlistat increases the expression of Pro-neuropeptide Y (NPY).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Pro-neuropeptide Y (NPY).	[11]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Pro-neuropeptide Y (NPY).	[4]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Pro-neuropeptide Y (NPY).	[13]
Linalool	DMGZQ5P	Investigative	Linalool increases the expression of Pro-neuropeptide Y (NPY).	[14]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Guanethidine	DM9NSWT	Approved	Guanethidine decreases the secretion of Pro-neuropeptide Y (NPY).	[10]

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 Pro-neuropeptide Y (NPY).	[12]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [3] Arsenic trioxide inhibits neuroblastoma growth in vivo and promotes apoptotic cell death in vitro. Biochem Biophys Res Commun. 2000 Oct 14;277(1):179-85. doi: 10.1006/bbrc.2000.3651.
• [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] Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer. BMC Cancer. 2007 Dec 11;7:223.
• [7] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [8] Neuropeptide Y in cortisol-induced hypertension in male volunteers. Clin Exp Pharmacol Physiol. 1994 May;21(5):435-8. doi: 10.1111/j.1440-1681.1994.tb02538.x.
• [9] [Effect of orlistat therapy on carbohydrate, lipid, vitamin and hormone plasma levels in obese subjects]. Pol Arch Med Wewn. 2004 Dec;112(6):1415-23.
• [10] Release and functional role of neuropeptide Y as a sympathetic modulator in human saphenous vein biopsies. Peptides. 2004 Jan;25(1):53-64. doi: 10.1016/j.peptides.2003.11.001.
• [11] 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.
• [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] 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.
• [14] In vitro neuropeptide Y mRNA expressing model for screening essences that may affect appetite using Rolf B1.T cells. J Agric Food Chem. 2012 Aug 15;60(32):7824-9. doi: 10.1021/jf302320f. Epub 2012 Aug 7.
• [15] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.