Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTRK9JT)

• DTT Name: Neuropeptide Y receptor type 1 (NPY1R)
• Synonyms: Neuropeptide Y-Y1 receptor; Neuropeptide Y receptor Y1; Neuropeptide Y Y(1) receptor; NPY1R; NPY1-R
• Gene Name: NPY1R
• DTT Type: Clinical trial target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: NPY1R_HUMAN
• TTD ID: T89213
• Sequence:
  MNSTLFSQVENHSVHSNFSEKNAQLLAFENDDCHLPLAMIFTLALAYGAVIILGVSGNLA
  LIIIILKQKEMRNVTNILIVNLSFSDLLVAIMCLPFTFVYTLMDHWVFGEAMCKLNPFVQ
  CVSITVSIFSLVLIAVERHQLIINPRGWRPNNRHAYVGIAVIWVLAVASSLPFLIYQVMT
  DEPFQNVTLDAYKDKYVCFDQFPSDSHRLSYTTLLLVLQYFGPLCFIFICYFKIYIRLKR
  RNNMMDKMRDNKYRSSETKRINIMLLSIVVAFAVCWLPLTIFNTVFDWNHQIIATCNHNL
  LFLLCHLTAMISTCVNPIFYGFLNKNFQRDLQFFFNFCDFRSRDDDYETIAMSTMHTDVS
  KTSLKQASPVAFKKINNNDDNEKI
• Function: Receptor for neuropeptide Y and peptide YY. The rank order of affinity of this receptor for pancreatic polypeptides is NPY > [Pro-34] PYY, PYY and [Leu-31, Pro-34] NPY > NPY (2-36) > [Ile-31, Gln-34] PP and PYY (3-36) > PP > NPY free acid.
• KEGG Pathway:
  cAMP signaling pathway (hsa04024)
  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

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
NEUROPEPTIDE-Y	DMINQP1	N. A.	N. A.	Phase 2	[1]

3 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
H-409/22	DMYJ9CF	Cardiovascular disease	BA00-BE2Z	Discontinued in Phase 2	[2]
BIBP 3226	DMYBR9D	Hypertension	BA00-BA04	Terminated	[4]
SR 120819A	DMETDFM	Eating disorder	6B82	Terminated	[5]

2 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GI-264879A	DM25N8B	Obesity	5B81	Preclinical	[3]
PD-160170	DMB9Z4C	Heart disease	BA41-BA42	Preclinical	[3]

20 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one	DMM9X0G	Discovery agent	N.A.	Investigative	[6]
AcPYY(22-36)	DMDEFPS	Discovery agent	N.A.	Investigative	[7]
Adp[-Trp-Arg-Nva-Arg-Tyr-NH2]2	DMVWM75	Discovery agent	N.A.	Investigative	[8]
BIBO3304	DML7HFP	Discovery agent	N.A.	Investigative	[9]
BMS-189323	DM7GUDC	Discovery agent	N.A.	Investigative	[10]
BMS-193885	DM1ZBU3	Discovery agent	N.A.	Investigative	[11]
BMS-245782	DM5SNMQ	Discovery agent	N.A.	Investigative	[10]
H-[Trp-Arg-Nva-Arg-Tyr]2-NH2	DM9XK05	Discovery agent	N.A.	Investigative	[8]
H-[Trp-Arg-Nva-Arg-Tyr]3-NH2	DMKH8PF	Discovery agent	N.A.	Investigative	[8]
J-104870	DMCS4BL	Discovery agent	N.A.	Investigative	[12]
LRHYLNLLTRQRY-NH2	DMY1807	Discovery agent	N.A.	Investigative	[13]
NPY-1 antagonist	DM1MOG8	Eating disorder	6B82	Investigative	[14]
Pim[-Trp-Arg-Nva-Arg-Tyr-NH2]2	DMBERSG	Discovery agent	N.A.	Investigative	[8]
PYY(22-36)	DM725FL	Discovery agent	N.A.	Investigative	[7]
S-19528	DM589XM	Eating disorder	6B82	Investigative	[14]
S-25585	DMBUD1M	Eating disorder	6B82	Investigative	[14]
Sub[-Trp-Arg-Nva-Arg-Tyr-NH2]2	DM4SWQA	Discovery agent	N.A.	Investigative	[8]
Sub[-Tyr-Arg-Leu-Arg-Tyr-NH2]2	DM56MOV	Discovery agent	N.A.	Investigative	[8]
[125I]GR231118	DMFWE4H	Discovery agent	N.A.	Investigative	[15]
[Cys-Trp-Arg-Nva-Arg-Tyr-NH2]2	DMWFGBC	Discovery agent	N.A.	Investigative	[8]

References

• [1] 5-OHKF and NorKA, depsipeptides from a Hawaiian collection of Bryopsis pennata: binding properties for NorKA to the human neuropeptide Y Y1 receptor. J Nat Prod. 2009 Dec;72(12):2172-6.
• [2] In vivo characterization of the novel neuropeptide Y Y1 receptor antagonist H 409/22. J Cardiovasc Pharmacol. 2000 Oct;36(4):516-25.
• [3] Emerging drugs for obesity: linking novel biological mechanisms to pharmaceutical pipelines. Expert Opin Emerg Drugs. 2005 Aug;10(3):643-60.
• [4] 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: 305).
• [5] SR 120819A, an orally-active and selective neuropeptide Y Y1 receptor antagonist. FEBS Lett. 1995 Apr 3;362(2):192-6.
• [6] Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 rec... J Med Chem. 2010 Sep 9;53(17):6386-97.
• [7] Identification of selective neuropeptide Y2 peptide agonists. Bioorg Med Chem Lett. 2007 Jan 15;17(2):538-41.
• [8] 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.
• [9] Neuropeptide Y induced modulation of dopamine synthesis in the striatum. Regul Pept. 2005 Jul 15;129(1-3):73-8.
• [10] Isosteric N-arylpiperazine replacements in a series of dihydropyridine NPY1 receptor antagonists. Bioorg Med Chem Lett. 2004 Dec 20;14(24):5975-8.
• [11] Dihydropyridine neuropeptide Y Y(1) receptor antagonists. Bioorg Med Chem Lett. 2002 Feb 11;12(3):379-82.
• [12] The novel neuropeptide Y Y(1) receptor antagonist J-104870: a potent feeding suppressant with oral bioavailability. Biochem Biophys Res Commun. 1999 Dec 9;266(1):88-91.
• [13] 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.
• [14] Emerging drugs for eating disorder treatment. Expert Opin Emerg Drugs. 2006 May;11(2):315-36.
• [15] [(125)I]-GR231118: a high affinity radioligand to investigate neuropeptide Y Y(1) and Y(4) receptors. Br J Pharmacol. 2000 Jan;129(1):37-46.