Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0LQH93)

• DOT Name: Pituitary adenylate cyclase-activating polypeptide (ADCYAP1)
• Synonyms: PACAP
• Gene Name: ADCYAP1
• UniProt ID: PACA_HUMAN
• PDB ID: 1GEA; 2D2P; 2JOD; 6LPB; 6M1I; 6P9Y; 6VN7; 7VQX; 7WBJ; 8E3X; 8E3Y
• Pfam ID: PF00123
• Sequence:
  MTMCSGARLALLVYGIIMHSSVYSSPAAAGLRFPGIRPEEEAYGEDGNPLPDFDGSEPPG
  AGSPASAPRAAAAWYRPAGRRDVAHGILNEAYRKVLDQLSAGKHLQSLVARGVGGSLGGG
  AGDDAEPLSKRHSDGIFTDSYSRYRKQMAVKKYLAAVLGKRYKQRVKNKGRRIAYL
• Function: Binding to its receptor activates G proteins and stimulates adenylate cyclase in pituitary cells. Promotes neuron projection development through the RAPGEF2/Rap1/B-Raf/ERK pathway. In chromaffin cells, induces long-lasting increase of intracellular calcium concentrations and neuroendocrine secretion. Involved in the control of glucose homeostasis, induces insulin secretion by pancreatic beta cells.
• KEGG Pathway:
  cAMP sig.ling pathway (hsa04024)
  Neuroactive ligand-receptor interaction (hsa04080)
  Circadian entrainment (hsa04713)
  Insulin secretion (hsa04911)
  Renin secretion (hsa04924)
• Reactome Pathway:
  G alpha (s) signalling events (R-HSA-418555)
  Glucagon-type ligand receptors (R-HSA-420092)
  NGF-independant TRKA activation (R-HSA-187024)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Progesterone	DMUY35B	Approved	Pituitary adenylate cyclase-activating polypeptide (ADCYAP1) increases the abundance of Progesterone.	[8]

9 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 Pituitary adenylate cyclase-activating polypeptide (ADCYAP1).	[1]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Pituitary adenylate cyclase-activating polypeptide (ADCYAP1).	[1]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Pituitary adenylate cyclase-activating polypeptide (ADCYAP1).	[4]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Pituitary adenylate cyclase-activating polypeptide (ADCYAP1).	[5]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Pituitary adenylate cyclase-activating polypeptide (ADCYAP1).	[6]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Pituitary adenylate cyclase-activating polypeptide (ADCYAP1).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Pituitary adenylate cyclase-activating polypeptide (ADCYAP1).	[1]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Pituitary adenylate cyclase-activating polypeptide (ADCYAP1).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Pituitary adenylate cyclase-activating polypeptide (ADCYAP1).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Pituitary adenylate cyclase-activating polypeptide (ADCYAP1).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Pituitary adenylate cyclase-activating polypeptide (ADCYAP1).	[3]

References

• [1] 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.
• [2] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] 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.
• [4] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [5] 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.
• [6] 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.
• [7] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [8] Luteinizing hormone-stimulated pituitary adenylate cyclase-activating polypeptide system and its role in progesterone production in human luteinized granulosa cells. Endocr J. 2010;57(2):127-34. doi: 10.1507/endocrj.k09e-077. Epub 2009 Nov 19.