Target Information
| Target General Information | Top | |||||
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| Target ID |
T67818
(Former ID: TTDR00081)
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| Target Name |
P2Y purinoceptor 1 (P2RY1)
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| Synonyms |
P2Y1; P2Y(1) receptor; P2RY1; Adenosine P2Y1 receptor
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| Gene Name |
P2RY1
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| Target Type |
Literature-reported target
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[1] | ||||
| 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.
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| BioChemical Class |
GPCR rhodopsin
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| UniProt ID | ||||||
| Sequence |
MTEVLWPAVPNGTDAAFLAGPGSSWGNSTVASTAAVSSSFKCALTKTGFQFYYLPAVYIL
VFIIGFLGNSVAIWMFVFHMKPWSGISVYMFNLALADFLYVLTLPALIFYYFNKTDWIFG DAMCKLQRFIFHVNLYGSILFLTCISAHRYSGVVYPLKSLGRLKKKNAICISVLVWLIVV VAISPILFYSGTGVRKNKTITCYDTTSDEYLRSYFIYSMCTTVAMFCVPLVLILGCYGLI VRALIYKDLDNSPLRRKSIYLVIIVLTVFAVSYIPFHVMKTMNLRARLDFQTPAMCAFND RVYATYQVTRGLASLNSCVDPILYFLAGDTFRRRLSRATRKASRRSEANLQSKSEDMTLN ILPEFKQNGDTSL Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T47DYR | |||||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Pathway Affiliation
Biological Network Descriptors
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Rap1 signaling pathway | hsa04015 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Neuroactive ligand-receptor interaction | hsa04080 | Affiliated Target |
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| Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
| Platelet activation | hsa04611 | Affiliated Target |
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| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| Taste transduction | hsa04742 | Affiliated Target |
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| Class: Organismal Systems => Sensory system | Pathway Hierarchy | ||
| Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
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| Closeness centrality | 1.86E-01 | Radiality | 1.31E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 5.20E+01 | Topological coefficient | 1.00E+00 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 3 KEGG Pathways | + | ||||
| 1 | Rap1 signaling pathway | |||||
| 2 | Neuroactive ligand-receptor interaction | |||||
| 3 | Platelet activation | |||||
| Reactome | [+] 3 Reactome Pathways | + | ||||
| 1 | G alpha (q) signalling events | |||||
| 2 | P2Y receptors | |||||
| 3 | ADP signalling through P2Y purinoceptor 1 | |||||
| WikiPathways | [+] 6 WikiPathways | + | ||||
| 1 | Nucleotide GPCRs | |||||
| 2 | GPCRs, Class A Rhodopsin-like | |||||
| 3 | Gastrin-CREB signalling pathway via PKC and MAPK | |||||
| 4 | Signal amplification | |||||
| 5 | GPCR ligand binding | |||||
| 6 | GPCR downstream signaling | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 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). | |||||
| REF 2 | P2Y1 receptor antagonists as novel antithrombotic agents. Bioorg Med Chem Lett. 2008 Jun 1;18(11):3338-43. | |||||
| REF 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. | |||||
| REF 4 | 2,2'-Pyridylisatogen tosylate antagonizes P2Y1 receptor signaling without affecting nucleotide binding. Biochem Pharmacol. 2004 Jul 15;68(2):231-7. | |||||
| REF 5 | ATP derivatives are antagonists of the P2Y1 receptor: similarities to the platelet ADP receptor. Mol Pharmacol. 1998 Apr;53(4):727-33. | |||||
| REF 6 | Highly efficient biocompatible neuroprotectants with dual activity as antioxidants and P2Y receptor agonists. J Med Chem. 2013 Jun 27;56(12):4938-52. | |||||
| REF 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. | |||||
| REF 8 | Quantitation of the P2Y(1) receptor with a high affinity radiolabeled antagonist. Mol Pharmacol. 2002 Nov;62(5):1249-57. | |||||
| REF 9 | Identification of competitive antagonists of the P2Y1 receptor. Mol Pharmacol. 1996 Nov;50(5):1323-9. | |||||
| REF 10 | New azole antagonists with high affinity for the P2Y(1) receptor. Bioorg Med Chem Lett. 2013 Jun 15;23(12):3519-22. | |||||
| REF 11 | Benzofuran-substituted urea derivatives as novel P2Y(1) receptor antagonists. Bioorg Med Chem Lett. 2010 Jul 15;20(14):4104-7. | |||||
| REF 12 | Tetrahydro-4-quinolinamines identified as novel P2Y(1) receptor antagonists. Bioorg Med Chem Lett. 2008 Dec 1;18(23):6222-6. | |||||
| REF 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. | |||||
| REF 14 | Inhibition of localized thrombosis in P2Y1-deficient mice and rodents treated with MRS2179, a P2Y1 receptor antagonist. J Thromb Haemost. 2003 Jun;1(6):1144-9. | |||||
| REF 15 | Antiaggregatory activity in human platelets of potent antagonists of the P2Y 1 receptor. Biochem Pharmacol. 2004 Nov 15;68(10):1995-2002. | |||||
| REF 16 | 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. | |||||
| REF 17 | 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. | |||||
| REF 18 | Virtual screening leads to the discovery of novel non-nucleotide P2Y receptor antagonists. Bioorg Med Chem. 2012 Sep 1;20(17):5254-61. | |||||
| REF 19 | 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. | |||||
| REF 20 | 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. | |||||
| REF 21 | Two disparate ligand-binding sites in the human P2Y1 receptor. Nature. 2015 Apr 16;520(7547):317-21. | |||||
| REF 22 | [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. | |||||
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