Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTA93TL)

• DTT Name: P2Y purinoceptor 1 (P2RY1)
• Synonyms: P2Y1; P2Y(1) receptor; P2RY1; Adenosine P2Y1 receptor
• Gene Name: P2RY1
• DTT Type: Literature-reported target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: P2RY1_HUMAN
• TTD ID: T67818
• Sequence:
  MTEVLWPAVPNGTDAAFLAGPGSSWGNSTVASTAAVSSSFKCALTKTGFQFYYLPAVYIL
  VFIIGFLGNSVAIWMFVFHMKPWSGISVYMFNLALADFLYVLTLPALIFYYFNKTDWIFG
  DAMCKLQRFIFHVNLYGSILFLTCISAHRYSGVVYPLKSLGRLKKKNAICISVLVWLIVV
  VAISPILFYSGTGVRKNKTITCYDTTSDEYLRSYFIYSMCTTVAMFCVPLVLILGCYGLI
  VRALIYKDLDNSPLRRKSIYLVIIVLTVFAVSYIPFHVMKTMNLRARLDFQTPAMCAFND
  RVYATYQVTRGLASLNSCVDPILYFLAGDTFRRRLSRATRKASRRSEANLQSKSEDMTLN
  ILPEFKQNGDTSL
• Function: Receptor for extracellular adenine nucleotides such as ATP and ADP. In platelets binding to ADP leads to mobilization of intracellular calcium ions via activation of phospholipase C, a change in platelet shape, and probably to platelet aggregation.
• KEGG Pathway:
  Rap1 signaling pathway (hsa04015)
  Neuroactive ligand-receptor interaction (hsa04080)
  Platelet activation (hsa04611)
• Reactome Pathway:
  P2Y receptors (R-HSA-417957)
  ADP signalling through P2Y purinoceptor 1 (R-HSA-418592)
  G alpha (q) signalling events (R-HSA-416476)

Molecular Interaction Atlas (MIA) of This DTT

30 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1-(3,4-dichlorophenyl)-3-(3,5-dichlorophenyl)urea	DMNOQ49	Discovery agent	N.A.	Investigative	[2]
2',3'-ddATP	DMOB7P6	Discovery agent	N.A.	Investigative	[3]
2,2'-pyridylisatogen tosylate	DMOQDBA	Discovery agent	N.A.	Investigative	[4]
2-chloroadenosine-5-triphosphate	DMQUDA9	Discovery agent	N.A.	Investigative	[5]
2-Cl-ADP(alpha-BH3)	DM4235F	Discovery agent	N.A.	Investigative	[6]
2MeSADP	DMGADQ1	Discovery agent	N.A.	Investigative	[7]
2MeSATP	DMUE0W6	Discovery agent	N.A.	Investigative	[8]
A2P5P	DMK4OD7	Discovery agent	N.A.	Investigative	[9]
adenosine diphosphate	DMFUHKP	N. A.	N. A.	Investigative	[8]
adenosine-3'-5'-bisphosphate	DMSOVFD	Discovery agent	N.A.	Investigative	[9]
ATPgammaS	DMXHQIN	Discovery agent	N.A.	Investigative	[3]
BMS compound 4c	DMR82WI	Discovery agent	N.A.	Investigative	[10]
dATPalphaS	DMRDX8U	Discovery agent	N.A.	Investigative	[3]
GlaxoSmithKline compound 5h	DMNEML0	Discovery agent	N.A.	Investigative	[11]
GlaxoSmithKline compound 6i	DM1UAWP	Discovery agent	N.A.	Investigative	[12]
MRS-2179	DMIVGHB	Discovery agent	N.A.	Investigative	[13]
MRS2279	DM0QGF3	Discovery agent	N.A.	Investigative	[8]
MRS2298	DMZ6EGA	Discovery agent	N.A.	Investigative	[14]
MRS2365	DM0CS3V	Discovery agent	N.A.	Investigative	[15]
MRS2496	DM0CAKS	Discovery agent	N.A.	Investigative	[14]
MRS2500	DMNGTOY	Discovery agent	N.A.	Investigative	[16]
MRS2950	DMDSB1F	Discovery agent	N.A.	Investigative	[17]
N-(6)-methyl-2'-deoxyadenosine-3',5'-bisphosphate	DMKWYMP	Discovery agent	N.A.	Investigative	[18]
PMID18445527C11	DMW7PQ8	Discovery agent	N.A.	Investigative	[2]
PMID18445527C67	DM7AXRF	Discovery agent	N.A.	Investigative	[2]
PMID22873688C3a	DMLUCSB	Discovery agent	N.A.	Investigative	[19]
PMID23368907C16	DMPHKJI	Discovery agent	N.A.	Investigative	[20]
PPADS	DMWHN3T	Discovery agent	N.A.	Investigative	[8]
[32P]MRS2500	DMEMVY5	Discovery agent	N.A.	Investigative	[21]
[35S]ADPbetaS	DMAYPTO	Discovery agent	N.A.	Investigative	[1]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 323).
• [2] P2Y1 receptor antagonists as novel antithrombotic agents. Bioorg Med Chem Lett. 2008 Jun 1;18(11):3338-43.
• [3] An examination of deoxyadenosine 5'(alpha-thio)triphosphate as a ligand to define P2Y receptors and its selectivity as a low potency partial agonist of the P2Y1 receptor. Br J Pharmacol. 1997 May;121(2):338-44.
• [4] 2,2'-Pyridylisatogen tosylate antagonizes P2Y1 receptor signaling without affecting nucleotide binding. Biochem Pharmacol. 2004 Jul 15;68(2):231-7.
• [5] ATP derivatives are antagonists of the P2Y1 receptor: similarities to the platelet ADP receptor. Mol Pharmacol. 1998 Apr;53(4):727-33.
• [6] Highly efficient biocompatible neuroprotectants with dual activity as antioxidants and P2Y receptor agonists. J Med Chem. 2013 Jun 27;56(12):4938-52.
• [7] Molecular cloning of the platelet P2T(AC) ADP receptor: pharmacological comparison with another ADP receptor, the P2Y(1) receptor. Mol Pharmacol. 2001 Sep;60(3):432-9.
• [8] Quantitation of the P2Y(1) receptor with a high affinity radiolabeled antagonist. Mol Pharmacol. 2002 Nov;62(5):1249-57.
• [9] Identification of competitive antagonists of the P2Y1 receptor. Mol Pharmacol. 1996 Nov;50(5):1323-9.
• [10] New azole antagonists with high affinity for the P2Y(1) receptor. Bioorg Med Chem Lett. 2013 Jun 15;23(12):3519-22.
• [11] Benzofuran-substituted urea derivatives as novel P2Y(1) receptor antagonists. Bioorg Med Chem Lett. 2010 Jul 15;20(14):4104-7.
• [12] Tetrahydro-4-quinolinamines identified as novel P2Y(1) receptor antagonists. Bioorg Med Chem Lett. 2008 Dec 1;18(23):6222-6.
• [13] The P2Y(1) receptor as a target for new antithrombotic drugs: a review of the P2Y(1) antagonist MRS-2179. Cardiovasc Drug Rev. 2003 Spring;21(1):67-76.
• [14] Antiaggregatory activity in human platelets of potent antagonists of the P2Y 1 receptor. Biochem Pharmacol. 2004 Nov 15;68(10):1995-2002.
• [15] Induction of novel agonist selectivity for the ADP-activated P2Y1 receptor versus the ADP-activated P2Y12 and P2Y13 receptors by conformational con... J Pharmacol Exp Ther. 2004 Dec;311(3):1038-43.
• [16] 2-Substitution of adenine nucleotide analogues containing a bicyclo[3.1.0]hexane ring system locked in a northern conformation: enhanced potency as P2Y1 receptor antagonists. J Med Chem. 2003 Nov 6;46(23):4974-87.
• [17] Virtual screening leads to the discovery of novel non-nucleotide P2Y receptor antagonists. Bioorg Med Chem. 2012 Sep 1;20(17):5254-61.
• [18] Key role of the P2Y(1) receptor in tissue factor-induced thrombin-dependent acute thromboembolism: studies in P2Y(1)-knockout mice and mice treated with a P2Y(1) antagonist. Circulation. 2001 Feb 6;103(5):718-23.
• [19] Identification of a promising drug candidate for the treatment of type 2 diabetes based on a P2Y(1) receptor agonist. J Med Chem. 2012 Sep 13;55(17):7623-35.
• [20] Two disparate ligand-binding sites in the human P2Y1 receptor. Nature. 2015 Apr 16;520(7547):317-21.
• [21] [32P]2-iodo-N6-methyl-(N)-methanocarba-2'-deoxyadenosine-3',5'-bisphosphate ([32P]MRS2500), a novel radioligand for quantification of native P2Y1 receptors. Br J Pharmacol. 2006 Mar;147(5):459-67.