Target Information
| Target General Information | Top | |||||
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| Target ID |
T20331
(Former ID: TTDC00089)
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| Target Name |
Neuropeptide Y receptor type 5 (NPY5R)
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| Synonyms |
Y5 receptor; Neuropeptide Y receptor Y5; Neuropeptide Y (NPY) Y(5) receptor; NPYY5; NPY5R; NPY5-R; NPY-Y5 receptor
Click to Show/Hide
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| Gene Name |
NPY5R
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| Target Type |
Discontinued target
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[1] | ||||
| Disease | [+] 5 Target-related Diseases | + | ||||
| 1 | Acute diabete complication [ICD-11: 5A2Y] | |||||
| 2 | Obesity [ICD-11: 5B80-5B81] | |||||
| 3 | Fungal infection [ICD-11: 1F29-1F2F] | |||||
| 4 | Binge eating disorder [ICD-11: 6B82] | |||||
| 5 | Depression [ICD-11: 6A70-6A7Z] | |||||
| Function |
Receptor for neuropeptide Y and peptide YY. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity. Seems to be associated with food intake. Could be involved in feeding disorders.
Click to Show/Hide
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| BioChemical Class |
GPCR rhodopsin
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| UniProt ID | ||||||
| Sequence |
MDLELDEYYNKTLATENNTAATRNSDFPVWDDYKSSVDDLQYFLIGLYTFVSLLGFMGNL
LILMALMKKRNQKTTVNFLIGNLAFSDILVVLFCSPFTLTSVLLDQWMFGKVMCHIMPFL QCVSVLVSTLILISIAIVRYHMIKHPISNNLTANHGYFLIATVWTLGFAICSPLPVFHSL VELQETFGSALLSSRYLCVESWPSDSYRIAFTISLLLVQYILPLVCLTVSHTSVCRSISC GLSNKENRLEENEMINLTLHPSKKSGPQVKLSGSHKWSYSFIKKHRRRYSKKTACVLPAP ERPSQENHSRILPENFGSVRSQLSSSSKFIPGVPTCFEIKPEENSDVHELRVKRSVTRIK KRSRSVFYRLTILILVFAVSWMPLHLFHVVTDFNDNLISNRHFKLVYCICHLLGMMSCCL NPILYGFLNNGIKADLVSLIHCLHM 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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| Discontinued Drug(s) | [+] 5 Discontinued Drugs | + | ||||
| 1 | CGP71683A | Drug Info | Discontinued in Phase 3 | Obesity | [2], [3] | |
| 2 | Velneperit | Drug Info | Discontinued in Phase 2 | Obesity | [4] | |
| 3 | Axovan-3 | Drug Info | Discontinued in Phase 1 | Obesity | [5] | |
| 4 | S-234462 | Drug Info | Discontinued in Phase 1 | Obesity | [6] | |
| 5 | RWJ-49815 | Drug Info | Terminated | Fungal infection | [7] | |
| Preclinical Drug(s) | [+] 3 Preclinical Drugs | + | ||||
| 1 | FR-79620 | Drug Info | Preclinical | Diabetic complication | [1] | |
| 2 | GW-594884A | Drug Info | Preclinical | Obesity | [1] | |
| 3 | NPY5RA-972 | Drug Info | Preclinical | Obesity | [1] | |
| Mode of Action | [+] 3 Modes of Action | + | ||||
| Antagonist | [+] 14 Antagonist drugs | + | ||||
| 1 | CGP71683A | Drug Info | [8], [9], [10] | |||
| 2 | Velneperit | Drug Info | [6] | |||
| 3 | Axovan-3 | Drug Info | [5] | |||
| 4 | S-234462 | Drug Info | [6] | |||
| 5 | FR-79620 | Drug Info | [1] | |||
| 6 | GW-594884A | Drug Info | [1] | |||
| 7 | NPY5RA-972 | Drug Info | [1] | |||
| 8 | RWJ-49815 | Drug Info | [5] | |||
| 9 | FMS586 | Drug Info | [14] | |||
| 10 | JCF 109 | Drug Info | [16] | |||
| 11 | L-152,804 | Drug Info | [17] | |||
| 12 | LU-AA33810 | Drug Info | [18] | |||
| 13 | S-19528 | Drug Info | [5] | |||
| 14 | S-25585 | Drug Info | [5] | |||
| Inhibitor | [+] 6 Inhibitor drugs | + | ||||
| 1 | 2,4,4-triphenylimidazoline | Drug Info | [11] | |||
| 2 | AR-129330 | Drug Info | [12] | |||
| 3 | FR-226928 | Drug Info | [15] | |||
| 4 | FR-230481 | Drug Info | [15] | |||
| 5 | FR-233118 | Drug Info | [15] | |||
| 6 | FR-73966 | Drug Info | [15] | |||
| Agonist | [+] 1 Agonist drugs | + | ||||
| 1 | Bis(31/31')[[Cys(31), Nva(34)]NPY(27-36)-NH(2)] | Drug Info | [13] | |||
| 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 Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
| 1 | Neuroactive ligand-receptor interaction | |||||
| Reactome | [+] 2 Reactome Pathways | + | ||||
| 1 | Peptide ligand-binding receptors | |||||
| 2 | G alpha (i) signalling events | |||||
| WikiPathways | [+] 4 WikiPathways | + | ||||
| 1 | GPCRs, Class A Rhodopsin-like | |||||
| 2 | Peptide GPCRs | |||||
| 3 | GPCR ligand binding | |||||
| 4 | GPCR downstream signaling | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| Target QSAR Model | ||||||
| References | Top | |||||
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| REF 1 | Emerging drugs for obesity: linking novel biological mechanisms to pharmaceutical pipelines. Expert Opin Emerg Drugs. 2005 Aug;10(3):643-60. | |||||
| REF 2 | 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. (Ligand id: 1562). | |||||
| 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 800010609) | |||||
| REF 4 | New and emerging drug molecules against obesity. J Cardiovasc Pharmacol Ther. 2014 Jan;19(1):65-76. | |||||
| REF 5 | Emerging drugs for eating disorder treatment. Expert Opin Emerg Drugs. 2006 May;11(2):315-36. | |||||
| REF 6 | Clinical pipeline report, company report or official report of Shionogi (2011). | |||||
| REF 7 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009390) | |||||
| REF 8 | Neuropeptide Y-induced enhancement of the evoked release of newly synthesized dopamine in rat striatum: mediation by Y2 receptors. Neuropharmacology. 2007 May;52(6):1396-402. | |||||
| REF 9 | Neuropeptide Y induced modulation of dopamine synthesis in the striatum. Regul Pept. 2005 Jul 15;129(1-3):73-8. | |||||
| REF 10 | Neuropeptide Y Y(5) receptor antagonist CGP71683A: the effects on food intake and anxiety-related behavior in the rat. Eur J Pharmacol. 2001 Mar 2;414(2-3):215-24. | |||||
| REF 11 | Discovery of substituted 2,4,4-triarylimidazoline derivatives as potent and selective neuropeptide Y Y5 receptor antagonists. Bioorg Med Chem Lett. 2009 Mar 15;19(6):1670-4. | |||||
| REF 12 | Lead optimization of 4-(dimethylamino)quinazolines, potent and selective antagonists for the melanin-concentrating hormone receptor 1. Bioorg Med Chem Lett. 2005 Sep 1;15(17):3853-6. | |||||
| REF 13 | Bis(31/31')[[Cys(31), Nva(34)]NPY(27-36)-NH(2)]: a neuropeptide Y (NPY) Y(5) receptor selective agonist with a latent stimulatory effect on food intake in rats. Peptides. 2002 Aug;23(8):1485-90. | |||||
| REF 14 | Pharmacological characterization and feeding-suppressive property of FMS586 [3-(5,6,7,8-tetrahydro-9-isopropyl-carbazol-3-yl)-1-methyl-1-(2-pyridin... J Pharmacol Exp Ther. 2006 May;317(2):562-70. | |||||
| REF 15 | Novel potent antagonists of human neuropeptide Y Y5 receptors. Part 3: 7-methoxy-1-hydroxy-1-substituted tetraline derivatives. Bioorg Med Chem Lett. 2002 Mar 11;12(5):799-802. | |||||
| REF 16 | Development and characterization of a highly selective neuropeptide Y Y5 receptor agonist radioligand: [125I][hPP1-17, Ala31, Aib32]NPY. Br J Pharmacol. 2003 Aug;139(7):1360-8. | |||||
| REF 17 | L-152,804: orally active and selective neuropeptide Y Y5 receptor antagonist. Biochem Biophys Res Commun. 2000 May 27;272(1):169-73. | |||||
| REF 18 | 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: 308). | |||||
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