Target Information
| Target General Information | Top | |||||
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| Target ID |
T90782
(Former ID: TTDR00731)
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| Target Name |
P2Y purinoceptor 6 (P2RY6)
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| Synonyms |
P2Y6; P2RY6; Adenosine P2Y6 receptor
Click to Show/Hide
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| Gene Name |
P2RY6
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Alzheimer disease [ICD-11: 8A20] | |||||
| Function |
Receptor for extracellular UDP > UTP > ATP. The activity of this receptor is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system.
Click to Show/Hide
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| BioChemical Class |
GPCR rhodopsin
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| UniProt ID | ||||||
| Sequence |
MEWDNGTGQALGLPPTTCVYRENFKQLLLPPVYSAVLAAGLPLNICVITQICTSRRALTR
TAVYTLNLALADLLYACSLPLLIYNYAQGDHWPFGDFACRLVRFLFYANLHGSILFLTCI SFQRYLGICHPLAPWHKRGGRRAAWLVCVAVWLAVTTQCLPTAIFAATGIQRNRTVCYDL SPPALATHYMPYGMALTVIGFLLPFAALLACYCLLACRLCRQDGPAEPVAQERRGKAARM AVVVAAAFAISFLPFHITKTAYLAVRSTPGVPCTVLEAFAAAYKGTRPFASANSVLDPIL FYFTQKKFRRRPHELLQKLTAKWQRQGR Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | GC021109 | Drug Info | Phase 1 | Alzheimer disease | [1], [2] | |
| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | INS 316 | Drug Info | Discontinued in Phase 3 | Lung cancer | [3] | |
| Mode of Action | [+] 3 Modes of Action | + | ||||
| Agonist | [+] 13 Agonist drugs | + | ||||
| 1 | GC021109 | Drug Info | [1], [2] | |||
| 2 | INS 316 | Drug Info | [4] | |||
| 3 | 2MeSATP | Drug Info | [4] | |||
| 4 | 3-phenacyl-UDP | Drug Info | [5] | |||
| 5 | 5BrUTP | Drug Info | [4] | |||
| 6 | adenosine diphosphate | Drug Info | [4] | |||
| 7 | INS48823 | Drug Info | [6] | |||
| 8 | MRS2693 | Drug Info | [8] | |||
| 9 | MRS2782 | Drug Info | [9] | |||
| 10 | MRS2957 | Drug Info | [10] | |||
| 11 | Rp-5-OMe-UDPalphaB | Drug Info | [12] | |||
| 12 | UDP-beta-S | Drug Info | [6] | |||
| 13 | Up3U | Drug Info | [6] | |||
| Antagonist | [+] 2 Antagonist drugs | + | ||||
| 1 | MRS2567 | Drug Info | [7] | |||
| 2 | MRS2578 | Drug Info | [7] | |||
| Inhibitor | [+] 2 Inhibitor drugs | + | ||||
| 1 | PSB-0952 | Drug Info | [11] | |||
| 2 | RB 2 | Drug Info | [11] | |||
| 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).
Human Similarity Proteins
Human Pathway Affiliation
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Neuroactive ligand-receptor interaction | hsa04080 | Affiliated Target |
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| Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
| 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 | [+] 1 KEGG Pathways | + | ||||
| 1 | Neuroactive ligand-receptor interaction | |||||
| Reactome | [+] 2 Reactome Pathways | + | ||||
| 1 | G alpha (q) signalling events | |||||
| 2 | P2Y receptors | |||||
| WikiPathways | [+] 5 WikiPathways | + | ||||
| 1 | Nucleotide GPCRs | |||||
| 2 | GPCRs, Class A Rhodopsin-like | |||||
| 3 | Gastrin-CREB signalling pathway via PKC and MAPK | |||||
| 4 | GPCR ligand binding | |||||
| 5 | GPCR downstream signaling | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 2 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 3 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008257) | |||||
| REF 4 | Cloning, functional expression and tissue distribution of the human P2Y6 receptor. Biochem Biophys Res Commun. 1996 May 15;222(2):303-8. | |||||
| REF 5 | Synthesis and structure-activity relationships of uracil nucleotide derivatives and analogues as agonists at human P2Y2, P2Y4, and P2Y6 receptors. J Med Chem. 2006 Nov 30;49(24):7076-87. | |||||
| REF 6 | P2 receptors activated by uracil nucleotides--an update. Curr Med Chem. 2006;13(3):289-312. | |||||
| REF 7 | Diisothiocyanate derivatives as potent, insurmountable antagonists of P2Y6 nucleotide receptors. Biochem Pharmacol. 2004 May 1;67(9):1763-70. | |||||
| REF 8 | Structure-activity relationships of uridine 5'-diphosphate analogues at the human P2Y6 receptor. J Med Chem. 2006 Sep 7;49(18):5532-43. | |||||
| REF 9 | Synthesis and potency of novel uracil nucleotides and derivatives as P2Y2 and P2Y6 receptor agonists. Bioorg Med Chem. 2008 Jun 15;16(12):6319-32. | |||||
| REF 10 | Pyrimidine ribonucleotides with enhanced selectivity as P2Y(6) receptor agonists: novel 4-alkyloxyimino, (S)-methanocarba, and 5'-triphosphate gamma-ester modifications. J Med Chem. 2010 Jun 10;53(11):4488-501. | |||||
| REF 11 | Development of potent and selective inhibitors of ecto-5'-nucleotidase based on an anthraquinone scaffold. J Med Chem. 2010 Mar 11;53(5):2076-86. | |||||
| REF 12 | 5-OMe-uridine-5'-O-(alpha-boranodiphosphate), a novel nucleotide derivative highly active at the human P2Y(6) receptor protects against death-receptor mediated glial apoptosis. Neurosci Lett. 2014 Aug 22;578:80-4. | |||||
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