Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: P2Y purinoceptor 6 (P2RY6)
• Synonyms: P2Y6; P2RY6; Adenosine P2Y6 receptor
• Gene Name: P2RY6
• DTT Type: Clinical trial target; [1]
• Related Disease: Alzheimer disease [ICD-11: 8A20]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: P2RY6_HUMAN
• TTD ID: T90782
• Sequence:
  MEWDNGTGQALGLPPTTCVYRENFKQLLLPPVYSAVLAAGLPLNICVITQICTSRRALTR
  TAVYTLNLALADLLYACSLPLLIYNYAQGDHWPFGDFACRLVRFLFYANLHGSILFLTCI
  SFQRYLGICHPLAPWHKRGGRRAAWLVCVAVWLAVTTQCLPTAIFAATGIQRNRTVCYDL
  SPPALATHYMPYGMALTVIGFLLPFAALLACYCLLACRLCRQDGPAEPVAQERRGKAARM
  AVVVAAAFAISFLPFHITKTAYLAVRSTPGVPCTVLEAFAAAYKGTRPFASANSVLDPIL
  FYFTQKKFRRRPHELLQKLTAKWQRQGR
• Function: Receptor for extracellular UDP > UTP > ATP. The activity of this receptor is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system.
• Reactome Pathway:
  P2Y receptors (R-HSA-417957)
  G alpha (q) signalling events (R-HSA-416476)

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
GC021109	DMQBEYV	Alzheimer disease	8A20	Phase 1	[1], [2]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
INS 316	DMTHMEI	Lung cancer	2C25.0	Discontinued in Phase 3	[3]

15 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2MeSATP	DMUE0W6	Discovery agent	N.A.	Investigative	[3]
3-phenacyl-UDP	DMOLZ65	Discovery agent	N.A.	Investigative	[4]
5BrUTP	DMEVRH4	Discovery agent	N.A.	Investigative	[3]
adenosine diphosphate	DMFUHKP	N. A.	N. A.	Investigative	[3]
INS48823	DMLZFTH	Discovery agent	N.A.	Investigative	[5]
MRS2567	DMUJEA9	Discovery agent	N.A.	Investigative	[6]
MRS2578	DMKMPS6	Discovery agent	N.A.	Investigative	[6]
MRS2693	DM2L3CJ	Discovery agent	N.A.	Investigative	[7]
MRS2782	DMZSO4R	Discovery agent	N.A.	Investigative	[8]
MRS2957	DMROQP6	Discovery agent	N.A.	Investigative	[9]
PSB-0952	DMW19LB	Discovery agent	N.A.	Investigative	[10]
RB 2	DMCEFUW	Discovery agent	N.A.	Investigative	[10]
Rp-5-OMe-UDPalphaB	DM03RIT	Discovery agent	N.A.	Investigative	[11]
UDP-beta-S	DMMWHAV	Discovery agent	N.A.	Investigative	[5]
Up3U	DMKQWSB	Discovery agent	N.A.	Investigative	[5]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] Cloning, functional expression and tissue distribution of the human P2Y6 receptor. Biochem Biophys Res Commun. 1996 May 15;222(2):303-8.
• [4] Synthesis and structure-activity relationships of uracil nucleotide derivatives and analogues as agonists at human P2Y2, P2Y4, and P2Y6 receptors. J Med Chem. 2006 Nov 30;49(24):7076-87.
• [5] P2 receptors activated by uracil nucleotides--an update. Curr Med Chem. 2006;13(3):289-312.
• [6] Diisothiocyanate derivatives as potent, insurmountable antagonists of P2Y6 nucleotide receptors. Biochem Pharmacol. 2004 May 1;67(9):1763-70.
• [7] Structure-activity relationships of uridine 5'-diphosphate analogues at the human P2Y6 receptor. J Med Chem. 2006 Sep 7;49(18):5532-43.
• [8] Synthesis and potency of novel uracil nucleotides and derivatives as P2Y2 and P2Y6 receptor agonists. Bioorg Med Chem. 2008 Jun 15;16(12):6319-32.
• [9] Pyrimidine ribonucleotides with enhanced selectivity as P2Y(6) receptor agonists: novel 4-alkyloxyimino, (S)-methanocarba, and 5'-triphosphate gamma-ester modifications. J Med Chem. 2010 Jun 10;53(11):4488-501.
• [10] Development of potent and selective inhibitors of ecto-5'-nucleotidase based on an anthraquinone scaffold. J Med Chem. 2010 Mar 11;53(5):2076-86.
• [11] 5-OMe-uridine-5'-O-(alpha-boranodiphosphate), a novel nucleotide derivative highly active at the human P2Y(6) receptor protects against death-receptor mediated glial apoptosis. Neurosci Lett. 2014 Aug 22;578:80-4.