Target Information
| Target General Information | Top | |||||
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| Target ID |
T82083
(Former ID: TTDI03439)
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| Target Name |
P2Y purinoceptor 4 (P2RY4)
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| Synonyms |
Uridine nucleotide receptor; UNR; P2Y4; P2P; NRU
Click to Show/Hide
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| Gene Name |
P2RY4
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| Target Type |
Discontinued target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Lung cancer [ICD-11: 2C25] | |||||
| Function |
Receptor for UTP and UDP coupled to G-proteins that activate a phosphatidylinositol-calcium second messenger system. Not activated by ATP or ADP.
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| UniProt ID | ||||||
| Sequence |
MASTESSLLRSLGLSPGPGSSEVELDCWFDEDFKFILLPVSYAVVFVLGLGLNAPTLWLF
IFRLRPWDATATYMFHLALSDTLYVLSLPTLIYYYAAHNHWPFGTEICKFVRFLFYWNLY CSVLFLTCISVHRYLGICHPLRALRWGRPRLAGLLCLAVWLVVAGCLVPNLFFVTTSNKG TTVLCHDTTRPEEFDHYVHFSSAVMGLLFGVPCLVTLVCYGLMARRLYQPLPGSAQSSSR LRSLRTIAVVLTVFAVCFVPFHITRTIYYLARLLEADCRVLNIVNVVYKVTRPLASANSC LDPVLYLLTGDKYRRQLRQLCGGGKPQPRTAASSLALVSLPEDSSCRWAATPQDSSCSTP RADRL Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T33BFJ | |||||
| Drugs and Modes of Action | Top | |||||
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| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | INS 316 | Drug Info | Discontinued in Phase 3 | Lung cancer | [2] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Agonist | [+] 9 Agonist drugs | + | ||||
| 1 | INS 316 | Drug Info | [1] | |||
| 2 | (N)methanocarba-UTP | Drug Info | [3] | |||
| 3 | 2-amino-uridine-5'-monophosphate | Drug Info | [4] | |||
| 4 | CTP | Drug Info | [1] | |||
| 5 | ITP | Drug Info | [1] | |||
| 6 | MRS2927 | Drug Info | [5] | |||
| 7 | MRS4062 | Drug Info | [5] | |||
| 8 | N4-phenylethoxycytidine-5'-triphosphate | Drug Info | [5] | |||
| 9 | UTPgammaS | Drug Info | [7] | |||
| Antagonist | [+] 1 Antagonist drugs | + | ||||
| 1 | PPADS | Drug Info | [6] | |||
| 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 | ||
| Taste transduction | hsa04742 | Affiliated Target |
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| Class: Organismal Systems => Sensory system | 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 | ||||||
| References | Top | |||||
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| REF 1 | ATP, an agonist at the rat P2Y(4) receptor, is an antagonist at the human P2Y(4) receptor. Mol Pharmacol. 2000 May;57(5):926-31. | |||||
| REF 2 | 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 3 | Methanocarba modification of uracil and adenine nucleotides: high potency of Northern ring conformation at P2Y1, P2Y2, P2Y4, and P2Y11 but not P2Y6 receptors. J Med Chem. 2002 Jan 3;45(1):208-18. | |||||
| REF 4 | Structural modifications of UMP, UDP, and UTP leading to subtype-selective agonists for P2Y2, P2Y4, and P2Y6 receptors. J Med Chem. 2011 Apr 28;54(8):2878-90. | |||||
| REF 5 | Pyrimidine nucleotides with 4-alkyloxyimino and terminal tetraphosphate delta-ester modifications as selective agonists of the P2Y(4) receptor. J Med Chem. 2011 Jun 23;54(12):4018-33. | |||||
| REF 6 | Development of selective agonists and antagonists of P2Y receptors. Purinergic Signal. 2009 Mar;5(1):75-89. | |||||
| REF 7 | Enzymatic synthesis of UTP gamma S, a potent hydrolysis resistant agonist of P2U-purinoceptors. Br J Pharmacol. 1996 Jan;117(1):203-9. | |||||
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