Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5DA9DY)

• DOT Name: Neuropeptide Y receptor type 1 (NPY1R)
• Synonyms: NPY1-R
• Gene Name: NPY1R
• UniProt ID: NPY1R_HUMAN
• PDB ID: 5ZBQ; 7VGX; 7X9A
• Pfam ID: PF00001
• Sequence:
  MNSTLFSQVENHSVHSNFSEKNAQLLAFENDDCHLPLAMIFTLALAYGAVIILGVSGNLA
  LIIIILKQKEMRNVTNILIVNLSFSDLLVAIMCLPFTFVYTLMDHWVFGEAMCKLNPFVQ
  CVSITVSIFSLVLIAVERHQLIINPRGWRPNNRHAYVGIAVIWVLAVASSLPFLIYQVMT
  DEPFQNVTLDAYKDKYVCFDQFPSDSHRLSYTTLLLVLQYFGPLCFIFICYFKIYIRLKR
  RNNMMDKMRDNKYRSSETKRINIMLLSIVVAFAVCWLPLTIFNTVFDWNHQIIATCNHNL
  LFLLCHLTAMISTCVNPIFYGFLNKNFQRDLQFFFNFCDFRSRDDDYETIAMSTMHTDVS
  KTSLKQASPVAFKKINNNDDNEKI
• Function: Receptor for neuropeptide Y and peptide YY. The rank order of affinity of this receptor for pancreatic polypeptides is NPY > [Pro-34] PYY, PYY and [Leu-31, Pro-34] NPY > NPY (2-36) > [Ile-31, Gln-34] PP and PYY (3-36) > PP > NPY free acid.
• KEGG Pathway:
  cAMP sig.ling pathway (hsa04024)
  Neuroactive ligand-receptor interaction (hsa04080)
  Regulation of lipolysis in adipocytes (hsa04923)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methamphetamine	DMPM4SK	Approved	Neuropeptide Y receptor type 1 (NPY1R) increases the response to substance of Methamphetamine.	[14]

12 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 Neuropeptide Y receptor type 1 (NPY1R).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Neuropeptide Y receptor type 1 (NPY1R).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Neuropeptide Y receptor type 1 (NPY1R).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Neuropeptide Y receptor type 1 (NPY1R).	[4]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Neuropeptide Y receptor type 1 (NPY1R).	[5]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Neuropeptide Y receptor type 1 (NPY1R).	[6]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Neuropeptide Y receptor type 1 (NPY1R).	[7]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of Neuropeptide Y receptor type 1 (NPY1R).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Neuropeptide Y receptor type 1 (NPY1R).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Neuropeptide Y receptor type 1 (NPY1R).	[11]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Neuropeptide Y receptor type 1 (NPY1R).	[12]
ORG2058	DMH1M6N	Investigative	ORG2058 decreases the expression of Neuropeptide Y receptor type 1 (NPY1R).	[13]

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 Neuropeptide Y receptor type 1 (NPY1R).	[9]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [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] Changes in protein tyrosine phosphatase type IVA member 1 and zinc finger protein 36 C3H type-like 1 expression demonstrate altered estrogen and progestin effect in medroxyprogesterone acetate-resistant and estrogen-independent breast cancer cell models. Steroids. 2009 Apr-May;74(4-5):404-9. doi: 10.1016/j.steroids.2008.12.005. Epub 2008 Dec 25.
• [5] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [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] 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.
• [8] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [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] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [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] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [13] The antiproliferative effects of progestins in T47D breast cancer cells are tempered by progestin induction of the ETS transcription factor Elf5. Mol Endocrinol. 2010 Jul;24(7):1380-92. doi: 10.1210/me.2009-0516. Epub 2010 Jun 2.
• [14] Association between neuropeptide Y gene and its receptor Y1 gene and methamphetamine dependence. Psychiatry Clin Neurosci. 2009 Jun;63(3):417-22. doi: 10.1111/j.1440-1819.2009.01961.x.