Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTY6EWA)

• DTT Name: Neuropeptide Y receptor type 5 (NPY5R)
• Synonyms: Y5 receptor; Neuropeptide Y receptor Y5; Neuropeptide Y (NPY) Y(5) receptor; NPYY5; NPY5R; NPY5-R; NPY-Y5 receptor
• Gene Name: NPY5R
• DTT Type: Discontinued target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: NPY5R_HUMAN
• TTD ID: T20331
• Sequence:
  MDLELDEYYNKTLATENNTAATRNSDFPVWDDYKSSVDDLQYFLIGLYTFVSLLGFMGNL
  LILMALMKKRNQKTTVNFLIGNLAFSDILVVLFCSPFTLTSVLLDQWMFGKVMCHIMPFL
  QCVSVLVSTLILISIAIVRYHMIKHPISNNLTANHGYFLIATVWTLGFAICSPLPVFHSL
  VELQETFGSALLSSRYLCVESWPSDSYRIAFTISLLLVQYILPLVCLTVSHTSVCRSISC
  GLSNKENRLEENEMINLTLHPSKKSGPQVKLSGSHKWSYSFIKKHRRRYSKKTACVLPAP
  ERPSQENHSRILPENFGSVRSQLSSSSKFIPGVPTCFEIKPEENSDVHELRVKRSVTRIK
  KRSRSVFYRLTILILVFAVSWMPLHLFHVVTDFNDNLISNRHFKLVYCICHLLGMMSCCL
  NPILYGFLNNGIKADLVSLIHCLHM
• 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.
• KEGG Pathway: Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DTT

5 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CGP71683A	DMRYC08	Obesity	5B81	Discontinued in Phase 3	[2]
Velneperit	DMROSHN	Obesity	5B81	Discontinued in Phase 2	[3]
Axovan-3	DM1JN6A	Eating disorder	6B82	Discontinued in Phase 1	[4]
S-234462	DM80P4U	Obesity	5B81	Discontinued in Phase 1	[3]
RWJ-49815	DMUGZMO	Fungal infection	1F29-1F2F	Terminated	[4]

3 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
FR-79620	DMXR287	Diabetic complication	5A2Y	Preclinical	[1]
GW-594884A	DMHUD27	Obesity	5B81	Preclinical	[1]
NPY5RA-972	DMXUCSN	Obesity	5B81	Preclinical	[1]

13 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2,4,4-triphenylimidazoline	DMS8I1E	Discovery agent	N.A.	Investigative	[5]
AR-129330	DMUSYKG	Discovery agent	N.A.	Investigative	[6]
Bis(31/31')[[Cys(31), Nva(34)]NPY(27-36)-NH(2)]	DMKANOH	Discovery agent	N.A.	Investigative	[7]
FMS586	DMQBTL3	Discovery agent	N.A.	Investigative	[8]
FR-226928	DMBY3T5	Discovery agent	N.A.	Investigative	[9]
FR-230481	DMKJQWR	Discovery agent	N.A.	Investigative	[9]
FR-233118	DMPD16N	Discovery agent	N.A.	Investigative	[9]
FR-73966	DMV0UM2	Discovery agent	N.A.	Investigative	[9]
JCF 109	DMYF7AE	Discovery agent	N.A.	Investigative	[10]
L-152,804	DMVGX7Z	Discovery agent	N.A.	Investigative	[11]
LU-AA33810	DM34AYV	Major depressive disorder	6A70.3	Investigative	[12]
S-19528	DM589XM	Eating disorder	6B82	Investigative	[4]
S-25585	DMBUD1M	Eating disorder	6B82	Investigative	[4]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Major depressive disorder	6A20	Pre-frontal cortex	7.49E-01	1.19E-02	0.03

References

• [1] Emerging drugs for obesity: linking novel biological mechanisms to pharmaceutical pipelines. Expert Opin Emerg Drugs. 2005 Aug;10(3):643-60.
• [2] 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.
• [3] Clinical pipeline report, company report or official report of Shionogi (2011).
• [4] Emerging drugs for eating disorder treatment. Expert Opin Emerg Drugs. 2006 May;11(2):315-36.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] L-152,804: orally active and selective neuropeptide Y Y5 receptor antagonist. Biochem Biophys Res Commun. 2000 May 27;272(1):169-73.
• [12] 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).