Target Information
| Target General Information | Top | |||||
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| Target ID |
T10670
(Former ID: TTDC00040)
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| Target Name |
Neuropeptide Y receptor type 2 (NPY2R)
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| Synonyms |
Y2 receptor; NPY2R; NPY2-R; NPY-Y2 receptor
Click to Show/Hide
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| Gene Name |
NPY2R
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 3 Target-related Diseases | + | ||||
| 1 | Obesity [ICD-11: 5B80-5B81] | |||||
| 2 | Acute diabete complication [ICD-11: 5A2Y] | |||||
| 3 | Metabolic disorder [ICD-11: 5C50-5D2Z] | |||||
| Function |
Receptor for neuropeptide Y andpeptide YY. The rank order of affinity of this receptor for pancreatic polypeptides is PYY > NPY > PYY (3-36) > NPY (2-36) > [Ile-31, Gln-34] PP > [Leu- 31, Pro-34] NPY > PP, [Pro-34] PYY and NPY free acid.
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| BioChemical Class |
GPCR rhodopsin
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| UniProt ID | ||||||
| Sequence |
MGPIGAEADENQTVEEMKVEQYGPQTTPRGELVPDPEPELIDSTKLIEVQVVLILAYCSI
ILLGVIGNSLVIHVVIKFKSMRTVTNFFIANLAVADLLVNTLCLPFTLTYTLMGEWKMGP VLCHLVPYAQGLAVQVSTITLTVIALDRHRCIVYHLESKISKRISFLIIGLAWGISALLA SPLAIFREYSLIEIIPDFEIVACTEKWPGEEKSIYGTVYSLSSLLILYVLPLGIISFSYT RIWSKLKNHVSPGAANDHYHQRRQKTTKMLVCVVVVFAVSWLPLHAFQLAVDIDSQVLDL KEYKLIFTVFHIIAMCSTFANPLLYGWMNSNYRKAFLSAFRCEQRLDAIHSEVSVTFKAK KNLEVRKNSGPNDSFTEATNV 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) | [+] 3 Discontinued Drugs | + | ||||
| 1 | PYY3-36 | Drug Info | Discontinued in Phase 2 | Obesity | [2], [3] | |
| 2 | TM30338 | Drug Info | Discontinued in Phase 2 | Obesity | [4] | |
| 3 | AC-162352 | Drug Info | Discontinued in Phase 1 | Obesity | [5] | |
| Preclinical Drug(s) | [+] 2 Preclinical Drugs | + | ||||
| 1 | BMS-192548 | Drug Info | Preclinical | Obesity | [5] | |
| 2 | CIN-110 | Drug Info | Preclinical | Obesity | [6] | |
| Mode of Action | [+] 4 Modes of Action | + | ||||
| Inhibitor | [+] 14 Inhibitor drugs | + | ||||
| 1 | NEUROPEPTIDE-Y | Drug Info | [1] | |||
| 2 | AcNPY(25-36) | Drug Info | [8] | |||
| 3 | AcPYY(22-36) | Drug Info | [8] | |||
| 4 | AcPYY(25-36) | Drug Info | [8] | |||
| 5 | AcPYY(26-36) | Drug Info | [8] | |||
| 6 | Adp[-Trp-Arg-Nva-Arg-Tyr-NH2]2 | Drug Info | [9] | |||
| 7 | H-[Trp-Arg-Nva-Arg-Tyr]2-NH2 | Drug Info | [9] | |||
| 8 | H-[Trp-Arg-Nva-Arg-Tyr]3-NH2 | Drug Info | [9] | |||
| 9 | LRHYLNLLTRQRY-NH2 | Drug Info | [12] | |||
| 10 | Pim[-Trp-Arg-Nva-Arg-Tyr-NH2]2 | Drug Info | [9] | |||
| 11 | PYY(22-36) | Drug Info | [8] | |||
| 12 | PYY(25-36) | Drug Info | [8] | |||
| 13 | Sub[-Trp-Arg-Nva-Arg-Tyr-NH2]2 | Drug Info | [9] | |||
| 14 | Sub[-Tyr-Arg-Leu-Arg-Tyr-NH2]2 | Drug Info | [9] | |||
| Agonist | [+] 4 Agonist drugs | + | ||||
| 1 | PYY3-36 | Drug Info | [5] | |||
| 2 | AC-162352 | Drug Info | [5] | |||
| 3 | CIN-110 | Drug Info | [6] | |||
| 4 | PD-4048 | Drug Info | [13] | |||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | TM30338 | Drug Info | [7] | |||
| 2 | PEGylated PYY-3-36 | Drug Info | [13] | |||
| Antagonist | [+] 3 Antagonist drugs | + | ||||
| 1 | BMS-192548 | Drug Info | [5] | |||
| 2 | BIIE0246 | Drug Info | [10] | |||
| 3 | JNJ-5207787 | 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).
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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| Neuroactive ligand-receptor interaction | hsa04080 | Affiliated Target |
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| Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
| Degree | 2 | Degree centrality | 2.15E-04 | Betweenness centrality | 1.01E-04 |
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| Closeness centrality | 1.58E-01 | Radiality | 1.23E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 5.00E+00 | Topological coefficient | 5.71E-01 | Eccentricity | 13 |
| 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 | [+] 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 | ||||||
| References | Top | |||||
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| REF 1 | cis-4-(Piperazin-1-yl)-5,6,7a,8,9,10,11,11a-octahydrobenzofuro[2,3-h]quinazolin-2-amine (A-987306), a new histamine H4R antagonist that blocks pain... J Med Chem. 2008 Nov 27;51(22):7094-8. | |||||
| 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: 1554). | |||||
| REF 3 | Emerging drugs for acute and chronic heart failure: current and future developments. Expert Opin Emerg Drugs. 2007 Mar;12(1):75-95. | |||||
| REF 4 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800023122) | |||||
| REF 5 | Emerging drugs for obesity: linking novel biological mechanisms to pharmaceutical pipelines. Expert Opin Emerg Drugs. 2005 Aug;10(3):643-60. | |||||
| REF 6 | Clinical pipeline report, company report or official report of CinFina Pharma | |||||
| REF 7 | Anti-Obesity Drug Discovery and Development, Atta-ur- Rahman, page(108) | |||||
| REF 8 | Identification of selective neuropeptide Y2 peptide agonists. Bioorg Med Chem Lett. 2007 Jan 15;17(2):538-41. | |||||
| REF 9 | Neuropeptide Y (NPY) Y4 receptor selective agonists based on NPY(32-36): development of an anorectic Y4 receptor selective agonist with picomolar a... J Med Chem. 2006 Apr 20;49(8):2661-5. | |||||
| REF 10 | The peptide YY-preferring receptor mediating inhibition of small intestinal secretion is a peripheral Y(2) receptor: pharmacological evidence and molecular cloning. Mol Pharmacol. 2001 Jul;60(1):124-34. | |||||
| REF 11 | Characterization of N-(1-Acetyl-2,3-dihydro-1H-indol-6-yl)-3-(3-cyano-phenyl)-N-[1-(2-cyclopentyl-ethyl)-piperidin-4yl]acrylamide (JNJ-5207787), a ... J Pharmacol Exp Ther. 2004 Mar;308(3):1130-7. | |||||
| REF 12 | A long-acting selective neuropeptide Y2 receptor PEGylated peptide agonist reduces food intake in mice. Bioorg Med Chem Lett. 2007 Apr 1;17(7):1916-9. | |||||
| REF 13 | 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: 306). | |||||
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