Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T46937
(Former ID: TTDS00113)
|
|||||
| Target 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
|
|||||
| Target Type |
Successful target
|
[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Myocardial infarction [ICD-11: BA41-BA43] | |||||
| 2 | Thrombosis [ICD-11: DB61-GB90] | |||||
| 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.
Click to Show/Hide
|
|||||
| BioChemical Class |
GPCR rhodopsin
|
|||||
| UniProt ID | ||||||
| Sequence |
MQAVDNLTSAPGNTSLCTRDYKITQVLFPLLYTVLFFVGLITNGLAMRIFFQIRSKSNFI
IFLKNTVISDLLMILTFPFKILSDAKLGTGPLRTFVCQVTSVIFYFTMYISISFLGLITI DRYQKTTRPFKTSNPKNLLGAKILSVVIWAFMFLLSLPNMILTNRQPRDKNVKKCSFLKS EFGLVWHEIVNYICQVIFWINFLIVIVCYTLITKELYRSYVRTRGVGKVPRKKVNVKVFI IIAVFFICFVPFHFARIPYTLSQTRDVFDCTAENTLFYVKESTLWLTSLNACLDPFIYFF LCKSFRNSLISMLKCPNSATSLSQDNRKKEQDGGDPNEETPM Click to Show/Hide
|
|||||
| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T82RFG | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 4 Approved Drugs | + | ||||
| 1 | Brilinta | Drug Info | Approved | Thrombosis | [2], [3] | |
| 2 | Cangrelor | Drug Info | Approved | Thrombosis | [4], [5] | |
| 3 | Clopidogrel | Drug Info | Approved | Thrombosis | [6], [7], [8] | |
| 4 | Prasugrel | Drug Info | Approved | Acute coronary syndrome | [9], [10] | |
| Clinical Trial Drug(s) | [+] 3 Clinical Trial Drugs | + | ||||
| 1 | INS-50589 | Drug Info | Phase 2 | Cardiovascular disease | [11], [12] | |
| 2 | ARL-67085 | Drug Info | Phase 1 | Thrombosis | [13], [14] | |
| 3 | Elinogrel | Drug Info | Phase 1 | Myocardial infarction | [15] | |
| Mode of Action | [+] 4 Modes of Action | + | ||||
| Antagonist | [+] 16 Antagonist drugs | + | ||||
| 1 | Brilinta | Drug Info | [8], [16] | |||
| 2 | Cangrelor | Drug Info | [8] | |||
| 3 | Clopidogrel | Drug Info | [1], [8] | |||
| 4 | Elinogrel | Drug Info | [18] | |||
| 5 | 2MeSAMP | Drug Info | [19] | |||
| 6 | ARL66096 | Drug Info | [20] | |||
| 7 | BX 048 | Drug Info | [21] | |||
| 8 | BX 667 | Drug Info | [21] | |||
| 9 | INS49266 | Drug Info | [22] | |||
| 10 | pCMPS | Drug Info | [1] | |||
| 11 | PMID22984835C20o | Drug Info | [23] | |||
| 12 | PMID22984835C4 | Drug Info | [23] | |||
| 13 | PMID23083103C4 | Drug Info | [24] | |||
| 14 | PRT-060096 | Drug Info | [8] | |||
| 15 | R-138727 | Drug Info | [26] | |||
| 16 | [3H]PSB-0413 | Drug Info | [27] | |||
| Inhibitor | [+] 3 Inhibitor drugs | + | ||||
| 1 | Prasugrel | Drug Info | [10] | |||
| 2 | PSB-0702 | Drug Info | [25] | |||
| 3 | PSB-0739 | Drug Info | [25] | |||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | INS-50589 | Drug Info | [17] | |||
| Agonist | [+] 3 Agonist drugs | + | ||||
| 1 | ARL-67085 | Drug Info | [14] | |||
| 2 | 2MeSADP | Drug Info | [1], [19] | |||
| 3 | adenosine diphosphate | Drug Info | [1] | |||
| Chemical Structure based Activity Landscape of Target | Top |
|---|---|
| Drug Property Profile of Target | Top | |
|---|---|---|
| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
|
|
||
| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
|
|
||
| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
|
|
||
| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target Affiliated Biological Pathways | Top | |||||
|---|---|---|---|---|---|---|
| KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
| 1 | Platelet activation | |||||
| Reactome | [+] 2 Reactome Pathways | + | ||||
| 1 | P2Y receptors | |||||
| 2 | G alpha (i) signalling events | |||||
| WikiPathways | [+] 4 WikiPathways | + | ||||
| 1 | GPCRs, Class A Rhodopsin-like | |||||
| 2 | Signal amplification | |||||
| 3 | GPCR ligand binding | |||||
| 4 | GPCR downstream signaling | |||||
| Target-Related Models and Studies | Top | |||||
|---|---|---|---|---|---|---|
| Target Validation | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | P2Y12, a new platelet ADP receptor, target of clopidogrel. Semin Vasc Med. 2003 May;3(2):113-22. | |||||
| REF 2 | 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. (Ligand id: 1765). | |||||
| REF 3 | 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4. | |||||
| REF 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. (Ligand id: 1776). | |||||
| REF 5 | ClinicalTrials.gov (NCT00385138) Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition.. U.S. National Institutes of Health. | |||||
| REF 6 | 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. (Ligand id: 7150). | |||||
| REF 7 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800029432) | |||||
| REF 8 | 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). | |||||
| REF 9 | 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. (Ligand id: 7562). | |||||
| REF 10 | Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92. | |||||
| REF 11 | 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. (Ligand id: 1770). | |||||
| REF 12 | ClinicalTrials.gov (NCT00316212) Study of INS50589 Intravenous Infusion in Subjects Undergoing Coronary Artery Bypass Grafting (CABG) Involving Cardiopulmonary Bypass. U.S. National Institutes of Health. | |||||
| REF 13 | 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. (Ligand id: 1756). | |||||
| REF 14 | Pharmacological characterization of the human P2Y11 receptor. Br J Pharmacol. 1999 Nov;128(6):1199-206. | |||||
| REF 15 | ClinicalTrials.gov (NCT00984113) Pharmacokinetics of Elinogrel in Healthy Volunteers and Patients With Mild, Moderate, and Severe Renal Impairment. U.S. National Institutes of Health. | |||||
| REF 16 | Clinical pipeline report, company report or official report of AstraZeneca (2009). | |||||
| REF 17 | 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. | |||||
| REF 18 | 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. | |||||
| REF 19 | 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. | |||||
| REF 20 | FPL 66096: a novel, highly potent and selective antagonist at human platelet P2T-purinoceptors. Br J Pharmacol. 1994 Nov;113(3):1057-63. | |||||
| REF 21 | Novel P2Y12 adenosine diphosphate receptor antagonists for inhibition of platelet aggregation (II): pharmacodynamic and pharmacokinetic characterization. Thromb Res. 2008;122(4):533-40. | |||||
| REF 22 | 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. | |||||
| REF 23 | Identification of high-affinity P2Y antagonists based on a phenylpyrazole glutamic acid piperazine backbone. J Med Chem. 2012 Oct 25;55(20):8615-29. | |||||
| REF 24 | 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. | |||||
| REF 25 | High-affinity, non-nucleotide-derived competitive antagonists of platelet P2Y12 receptors. J Med Chem. 2009 Jun 25;52(12):3784-93. | |||||
| REF 26 | 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. | |||||
| REF 27 | 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. | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.