Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTZ1DT0)

• DTT Name: P2Y purinoceptor 12 (P2RY12)
• Synonyms: SP1999; P2Y12 platelet ADP receptor; P2Y12; P2Y(cyc); P2Y(ADP)P2Y purinoceptor 12; P2Y(ADP); P2Y(AC); P2T(AC); P2RY12; Nucleotide P2Y(12) receptor; Adenosine P2Y12 receptor; ADPG-R; ADP-glucose receptor
• Gene Name: P2RY12
• DTT Type: Successful target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: P2Y12_HUMAN
• TTD ID: T46937
• Sequence:
  MQAVDNLTSAPGNTSLCTRDYKITQVLFPLLYTVLFFVGLITNGLAMRIFFQIRSKSNFI
  IFLKNTVISDLLMILTFPFKILSDAKLGTGPLRTFVCQVTSVIFYFTMYISISFLGLITI
  DRYQKTTRPFKTSNPKNLLGAKILSVVIWAFMFLLSLPNMILTNRQPRDKNVKKCSFLKS
  EFGLVWHEIVNYICQVIFWINFLIVIVCYTLITKELYRSYVRTRGVGKVPRKKVNVKVFI
  IIAVFFICFVPFHFARIPYTLSQTRDVFDCTAENTLFYVKESTLWLTSLNACLDPFIYFF
  LCKSFRNSLISMLKCPNSATSLSQDNRKKEQDGGDPNEETPM
• Function: Receptor for ADP and ATP coupled to G-proteins that inhibit the adenylyl cyclase second messenger system. Not activated by UDP and UTP. Required for normal platelet aggregation and blood coagulation.
• KEGG Pathway: Platelet activation (hsa04611)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  P2Y receptors (R-HSA-417957)

Molecular Interaction Atlas (MIA) of This DTT

4 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Brilinta	DMBR01X	Acute coronary syndrome	BA41	Approved	[2]
Cangrelor	DM8JRH0	Thrombosis	DB61-GB90	Approved	[3]
Clopidogrel	DMOL54H	Acute coronary syndrome	BA41	Approved	[1]
Prasugrel	DM7MT6E	Acute coronary syndrome	BA41	Approved	[4]

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
INS-50589	DMKZUVC	Cardiovascular disease	BA00-BE2Z	Phase 2	[5]
ARL-67085	DMY5IM2	Thrombosis	DB61-GB90	Phase 1	[6]
Elinogrel	DMA4BRV	Myocardial infarction	BA41-BA43	Phase 1	[7]

16 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2MeSADP	DMGADQ1	Discovery agent	N.A.	Investigative	[8]
2MeSAMP	DMBO2DC	Discovery agent	N.A.	Investigative	[8]
adenosine diphosphate	DMFUHKP	N. A.	N. A.	Investigative	[1]
ARL66096	DMNPEM4	Discovery agent	N.A.	Investigative	[9]
BX 048	DMA2B1C	Discovery agent	N.A.	Investigative	[10]
BX 667	DMBKVN9	Discovery agent	N.A.	Investigative	[10]
INS49266	DM95BL8	Discovery agent	N.A.	Investigative	[11]
pCMPS	DMGIS5Q	Discovery agent	N.A.	Investigative	[1]
PMID22984835C20o	DMAW86U	Discovery agent	N.A.	Investigative	[12]
PMID22984835C4	DMMI9JE	Discovery agent	N.A.	Investigative	[12]
PMID23083103C4	DMW579R	Discovery agent	N.A.	Investigative	[13]
PRT-060096	DM25EDB	Cardiovascular disease	BA00-BE2Z	Investigative	[3]
PSB-0702	DMLAFJE	Discovery agent	N.A.	Investigative	[14]
PSB-0739	DM3AZPD	Discovery agent	N.A.	Investigative	[14]
R-138727	DML49FI	Discovery agent	N.A.	Investigative	[15]
[3H]PSB-0413	DMP98AQ	Discovery agent	N.A.	Investigative	[16]

References

• [1] P2Y12, a new platelet ADP receptor, target of clopidogrel. Semin Vasc Med. 2003 May;3(2):113-22.
• [2] Clinical pipeline report, company report or official report of AstraZeneca (2009).
• [3] 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: 328).
• [4] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [5] Rapid and reversible modulation of platelet function in man by a novel P2Y(12) ADP-receptor antagonist, INS50589. Platelets. 2007 Aug;18(5):346-56.
• [6] Pharmacological characterization of the human P2Y11 receptor. Br J Pharmacol. 1999 Nov;128(6):1199-206.
• [7] Elinogrel, a reversible P2Y12 receptor antagonist for the treatment of acute coronary syndrome and prevention of secondary thrombotic events. Curr Opin Investig Drugs. 2010 Mar;11(3):340-8.
• [8] Molecular cloning of the platelet P2T(AC) ADP receptor: pharmacological comparison with another ADP receptor, the P2Y(1) receptor. Mol Pharmacol. 2001 Sep;60(3):432-9.
• [9] FPL 66096: a novel, highly potent and selective antagonist at human platelet P2T-purinoceptors. Br J Pharmacol. 1994 Nov;113(3):1057-63.
• [10] Novel P2Y12 adenosine diphosphate receptor antagonists for inhibition of platelet aggregation (II): pharmacodynamic and pharmacokinetic characterization. Thromb Res. 2008;122(4):533-40.
• [11] Lipophilic modifications to dinucleoside polyphosphates and nucleotides that confer antagonist properties at the platelet P2Y12 receptor. J Med Chem. 2008 Feb 28;51(4):1007-25.
• [12] Identification of high-affinity P2Y antagonists based on a phenylpyrazole glutamic acid piperazine backbone. J Med Chem. 2012 Oct 25;55(20):8615-29.
• [13] Modified diadenosine tetraphosphates with dual specificity for P2Y1 and P2Y12 are potent antagonists of ADP-induced platelet activation. J Thromb Haemost. 2012 Dec;10(12):2573-80.
• [14] High-affinity, non-nucleotide-derived competitive antagonists of platelet P2Y12 receptors. J Med Chem. 2009 Jun 25;52(12):3784-93.
• [15] Stereoselective inhibition of human platelet aggregation by R-138727, the active metabolite of CS-747 (prasugrel, LY640315), a novel P2Y12 receptor inhibitor. Thromb Haemost. 2005 Sep;94(3):593-8.
• [16] Synthesis and preliminary evaluation of [3H]PSB-0413, a selective antagonist radioligand for platelet P2Y12 receptors. Bioorg Med Chem Lett. 2005 Dec 15;15(24):5450-2.