Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXX6AF5)

• DOT Name: Peptide YY (PYY)
• Synonyms: PYY; PYY-I; Peptide tyrosine tyrosine
• Gene Name: PYY
• UniProt ID: PYY_HUMAN
• PDB ID: 2DEZ; 2DF0; 2L60; 2NA5; 7RT9; 7YON
• Pfam ID: PF00159
• Sequence:
  MVFVRRPWPALTTVLLALLVCLGALVDAYPIKPEAPREDASPEELNRYYASLRHYLNLVT
  RQRYGKRDGPDTLLSKTFFPDGEDRPVRSRSEGPDLW
• Function: This gut peptide inhibits exocrine pancreatic secretion, has a vasoconstrictory action and inhibitis jejunal and colonic mobility.
• 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

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Peptide YY (PYY).	[1]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Peptide YY (PYY).	[1]
Ibuprofen	DM8VCBE	Approved	Ibuprofen decreases the expression of Peptide YY (PYY).	[3]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Peptide YY (PYY).	[5]

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 Peptide YY (PYY).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Peptide YY (PYY).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Orlistat	DMRJSP8	Approved	Orlistat decreases the secretion of Peptide YY (PYY).	[4]

References

• [1] 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.
• [2] 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.
• [3] Rofecoxib modulates multiple gene expression pathways in a clinical model of acute inflammatory pain. Pain. 2007 Mar;128(1-2):136-47.
• [4] Orlistat inhibition of intestinal lipase acutely increases appetite and attenuates postprandial glucagon-like peptide-1-(7-36)-amide-1, cholecystokinin, and peptide YY concentrations. J Clin Endocrinol Metab. 2008 Oct;93(10):3995-8. doi: 10.1210/jc.2008-0924. Epub 2008 Jul 22.
• [5] 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.
• [6] 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.