Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTJ6WK9)

• DTT Name: Neuropeptide Y receptor type 2 (NPY2R)
• Synonyms: Y2 receptor; NPY2R; NPY2-R; NPY-Y2 receptor
• Gene Name: NPY2R
• DTT Type: Clinical trial target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: NPY2R_HUMAN
• TTD ID: T10670
• Sequence:
  MGPIGAEADENQTVEEMKVEQYGPQTTPRGELVPDPEPELIDSTKLIEVQVVLILAYCSI
  ILLGVIGNSLVIHVVIKFKSMRTVTNFFIANLAVADLLVNTLCLPFTLTYTLMGEWKMGP
  VLCHLVPYAQGLAVQVSTITLTVIALDRHRCIVYHLESKISKRISFLIIGLAWGISALLA
  SPLAIFREYSLIEIIPDFEIVACTEKWPGEEKSIYGTVYSLSSLLILYVLPLGIISFSYT
  RIWSKLKNHVSPGAANDHYHQRRQKTTKMLVCVVVVFAVSWLPLHAFQLAVDIDSQVLDL
  KEYKLIFTVFHIIAMCSTFANPLLYGWMNSNYRKAFLSAFRCEQRLDAIHSEVSVTFKAK
  KNLEVRKNSGPNDSFTEATNV
• 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.
• 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

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
PYY3-36	DMTGFV6	Obesity	5B81	Discontinued in Phase 2	[2]
TM30338	DMXNQLU	Obesity	5B81	Discontinued in Phase 2	[3]
AC-162352	DME98LV	Obesity	5B81	Discontinued in Phase 1	[2]

2 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BMS-192548	DMHAWBR	Obesity	5B81	Preclinical	[2]
CIN-110	DMYMZQW	Obesity	5B81	Preclinical	[4]

17 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AcNPY(25-36)	DMZBOQW	Discovery agent	N.A.	Investigative	[5]
AcPYY(22-36)	DMDEFPS	Discovery agent	N.A.	Investigative	[5]
AcPYY(25-36)	DMRSU2K	Discovery agent	N.A.	Investigative	[5]
AcPYY(26-36)	DM7RELC	Discovery agent	N.A.	Investigative	[5]
Adp[-Trp-Arg-Nva-Arg-Tyr-NH2]2	DMVWM75	Discovery agent	N.A.	Investigative	[6]
BIIE0246	DMR2SEB	Discovery agent	N.A.	Investigative	[7]
H-[Trp-Arg-Nva-Arg-Tyr]2-NH2	DM9XK05	Discovery agent	N.A.	Investigative	[6]
H-[Trp-Arg-Nva-Arg-Tyr]3-NH2	DMKH8PF	Discovery agent	N.A.	Investigative	[6]
JNJ-5207787	DMWYU5C	Discovery agent	N.A.	Investigative	[8]
LRHYLNLLTRQRY-NH2	DMY1807	Discovery agent	N.A.	Investigative	[9]
PD-4048	DM0OEH3	Diabetic complication	5A2Y	Investigative	[10]
PEGylated PYY-3-36	DM6K3G7	Metabolic disorder	5C50-5D2Z	Investigative	[10]
Pim[-Trp-Arg-Nva-Arg-Tyr-NH2]2	DMBERSG	Discovery agent	N.A.	Investigative	[6]
PYY(22-36)	DM725FL	Discovery agent	N.A.	Investigative	[5]
PYY(25-36)	DMD6ZWV	Discovery agent	N.A.	Investigative	[5]
Sub[-Trp-Arg-Nva-Arg-Tyr-NH2]2	DM4SWQA	Discovery agent	N.A.	Investigative	[6]
Sub[-Tyr-Arg-Leu-Arg-Tyr-NH2]2	DM56MOV	Discovery agent	N.A.	Investigative	[6]

References

• [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.
• [2] Emerging drugs for obesity: linking novel biological mechanisms to pharmaceutical pipelines. Expert Opin Emerg Drugs. 2005 Aug;10(3):643-60.
• [3] Anti-Obesity Drug Discovery and Development, Atta-ur- Rahman, page(108)
• [4] Clinical pipeline report, company report or official report of CinFina Pharma
• [5] Identification of selective neuropeptide Y2 peptide agonists. Bioorg Med Chem Lett. 2007 Jan 15;17(2):538-41.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] 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).