Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT47XN46)

• DOT Name: P2Y purinoceptor 2 (P2RY2)
• Synonyms: P2Y2; ATP receptor; P2U purinoceptor 1; P2U1; P2U receptor 1; Purinergic receptor
• Gene Name: P2RY2
• UniProt ID: P2RY2_HUMAN
• Pfam ID: PF00001
• Sequence:
  MAADLGPWNDTINGTWDGDELGYRCRFNEDFKYVLLPVSYGVVCVPGLCLNAVALYIFLC
  RLKTWNASTTYMFHLAVSDALYAASLPLLVYYYARGDHWPFSTVLCKLVRFLFYTNLYCS
  ILFLTCISVHRCLGVLRPLRSLRWGRARYARRVAGAVWVLVLACQAPVLYFVTTSARGGR
  VTCHDTSAPELFSRFVAYSSVMLGLLFAVPFAVILVCYVLMARRLLKPAYGTSGGLPRAK
  RKSVRTIAVVLAVFALCFLPFHVTRTLYYSFRSLDLSCHTLNAINMAYKVTRPLASANSC
  LDPVLYFLAGQRLVRFARDAKPPTGPSPATPARRRLGLRRSDRTDMQRIEDVLGSSEDSR
  RTESTPAGSENTKDIRL
• Function: Receptor for ATP and UTP coupled to G-proteins that activate a phosphatidylinositol-calcium second messenger system. The affinity range is UTP = ATP > ATP-gamma-S >> 2-methylthio-ATP = ADP.
• Tissue Specificity: Spleen, testis, kidney, liver, lung, heart and brain.
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Efferocytosis (hsa04148)
  Inflammatory mediator regulation of TRP channels (hsa04750)
• Reactome Pathway:
  P2Y receptors (R-HSA-417957)
  Surfactant metabolism (R-HSA-5683826)
  G alpha (q) signalling events (R-HSA-416476)

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
Chlorothiazide	DMLHESP	Approved	P2Y purinoceptor 2 (P2RY2) increases the Insomnia ADR of Chlorothiazide.	[16]

15 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 P2Y purinoceptor 2 (P2RY2).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of P2Y purinoceptor 2 (P2RY2).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of P2Y purinoceptor 2 (P2RY2).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of P2Y purinoceptor 2 (P2RY2).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of P2Y purinoceptor 2 (P2RY2).	[5]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of P2Y purinoceptor 2 (P2RY2).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of P2Y purinoceptor 2 (P2RY2).	[2]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of P2Y purinoceptor 2 (P2RY2).	[7]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide decreases the expression of P2Y purinoceptor 2 (P2RY2).	[8]
Adenosine triphosphate	DM79F6G	Approved	Adenosine triphosphate increases the activity of P2Y purinoceptor 2 (P2RY2).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of P2Y purinoceptor 2 (P2RY2).	[10]
PAI-1	DMY2AEF	Phase 4	PAI-1 decreases the expression of P2Y purinoceptor 2 (P2RY2).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of P2Y purinoceptor 2 (P2RY2).	[13]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of P2Y purinoceptor 2 (P2RY2).	[14]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of P2Y purinoceptor 2 (P2RY2).	[15]

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 P2Y purinoceptor 2 (P2RY2).	[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] Comparison of the gene expression profiles of monocytic versus granulocytic lineages of HL-60 leukemia cell differentiation by DNA microarray analysis. Life Sci. 2003 Aug 15;73(13):1705-19. doi: 10.1016/s0024-3205(03)00515-0.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [5] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [6] Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
• [7] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [8] Comparative gene expression analysis of a chronic myelogenous leukemia cell line resistant to cyclophosphamide using oligonucleotide arrays and response to tyrosine kinase inhibitors. Leuk Res. 2007 Nov;31(11):1511-20.
• [9] Regional differences in functional receptor distribution and calcium mobilization in the intact human lens. Invest Ophthalmol Vis Sci. 2001 Sep;42(10):2355-63.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Pseudomonas aeruginosa quorum-sensing signal molecule N-(3-oxododecanoyl)-L-homoserine lactone inhibits expression of P2Y receptors in cystic fibrosis tracheal gland cells. Infect Immun. 1999 Oct;67(10):5076-82. doi: 10.1128/IAI.67.10.5076-5082.1999.
• [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] Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.
• [14] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [15] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [16] A genome-wide association study of caffeine-related sleep disturbance: confirmation of a role for a common variant in the adenosine receptor. Sleep. 2012 Jul 1;35(7):967-75. doi: 10.5665/sleep.1962.