Stereoselective inhibition of human platelet aggregation by R-138727, the active metabolite of CS-747 (Prasugrel, LY640315), a novel P2Y12 receptor inhibitor

Thrombosis and Haemostasis

Volumn 94, Issue 3, 2005, Pages 593-598

  Hasegawa, Michihiro ^a   Sugidachi, Atsuhiro ^a   Ogawa, Taketoshi ^a   Isobe, Takashi ^a   Jakubowski, Joseph A ^b   Asai, Fumitoshi ^a  

^a DAIICHI SANKYO CO   (Japan)

^b ELI LILLY AND COMPANY   (United States)

Author keywords

ADP; P2Y12 receptors; Platelet aggregation; Prasugrel; Thienopyridine

Indexed keywords

1 [2 CYCLOPROPYL 1 (2 FLUOROPHENYL) 2 OXOETHYL] 4 MERCAPTO 3 PIPERIDINYLIDENE; 2 METHYLTHIOADENOSINE 5' DIPHOSPHATE; 2' DEOXY 6 N METHYLADENOSINE 3',5' BISPHOSPHATE; [1 [2 CYCLOPROPYL 1 (2 FLUOROPHENYL) 2 OXOETHYL] 4 MERCAPTO 3 PIPERIDINYLIDENE]TRIFLUOROACETIC ACID; ADENOSINE DIPHOSPHATE; ANTITHROMBOCYTIC AGENT; PRASUGREL; PURINE P2Y12 RECEPTOR; PURINERGIC RECEPTOR BLOCKING AGENT; R 100364; R 125687; R 125688; R 125689; R 125690; R 138727; R 99224; THIOL GROUP; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; BINDING ASSAY; CHO CELL; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG MECHANISM; DRUG POTENCY; DRUG RECEPTOR BINDING; HUMAN; HUMAN CELL; IN VITRO STUDY; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; STEREOCHEMISTRY; STEREOISOMERISM; STRUCTURE ACTIVITY RELATION; THROMBOCYTE AGGREGATION INHIBITION;

ANIMALS; BINDING, COMPETITIVE; BLOOD PLATELETS; CHO CELLS; CRICETINAE; CRICETULUS; CYCLOPROPANES; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; MEMBRANE PROTEINS; PIPERAZINES; PIPERIDINES; PLATELET AGGREGATION; PLATELET AGGREGATION INHIBITORS; PRODRUGS; RECEPTORS, PURINERGIC P2; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; THIOPHENES; TIME FACTORS; TRANSFECTION;

EID: 24944503641     PISSN: 03406245     EISSN: None     Source Type: Journal    
DOI: 10.1160/TH05-03-0208     Document Type: Article

References (26)

1. Gachet C. Identification, characterization, and inhibition of the platelet ADP receptors. Int J Hematol 2001; 74: 375-81.
2. Hollopeter G, Jantzen HM, Vincent D et al. Identification of the platelet ADP receptor targeted by anti-thrombotic drugs. Nature 2001; 11: 202-7.
3. 1-linked P2T antagonist, CS-747. Br J Pharmacol 2001; 132: 47-54.
4. 12 regulates platelet adhesion/activation, thrombus growth, and thrombus stability in injured arteries. J Clin Invest 2003; 112: 398-406.
5. Foster CJ, Prosser DM, Agans JM et al. Molecular identification and characterization of the platelet ADP receptor targeted by thienopyridine antithrombotic drugs. J Clin Invest 2001; 107: 1591-8.
6. 12 receptor in platelet activation. J Clin Invest 2004; 113: 340-5.
7. 12 receptor in thrombosis. Curr Opin Hematol 2003; 10: 333-8.
8. Gent M, Blakely JA, Easton JD et al. The Canadian American Ticlopidine Study (CATS) in thromboembolic stroke. Lancet 1989; 1: 1215-20.
9. Hass WK, Easton JD, Adams HP et al. A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. Ticlopidine Aspirin Stroke Study Group. New Engl J Med 1989; 321: 501-7.
10. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996; 348: 1329-39.
11. The CURE Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST segment elevation. N Engl J Med 2001; 345: 494-502.
12. Savi P, Pereillo JM, Uzabiaga MF et al. Identification and biological activity of the active metabolite of clopidogrel. Thromb Haemost 2000; 84: 891-6.
13. Sugidachi A, Asai F, Ogawa T et al. The in vivo pharmacological profile of CS-747, a novel antiplatelet agent with platelet ADP receptor antagonist properties. Br J Pharmacol 2000; 129: 1439-46.
14. Kazui M, Ishizuka T, Yamamura N et al. Mechanism for production of pharmacologically active metabolites of CS-747, a new pro-drug ADP-receptor antagonist. Thromb Haemost 2001; 86 (suppl.): P1916.
15. 1 receptor antagonist. Eur J Pharmacol 2001; 412: 213-21.
16. Sugidachi A, Ogawa T, Asai F et al. Inhibition of rat platelet aggregation by mycalolide-B, a novel inhibitor of actin polymerization with a different mechanism of action from cytochalasin-D. Thromb Haemost 1998; 79: 614-9.
17. 6-methyl 2′-deoxyadenosine 3′,5′-bisphosphate. Br J Pharmacol 1998; 124: 1-3.
18. Kunapuli SP, Ding Z, Dorsam RT et al. ADP receptors-targets for developing antithrombotic agents. Curr Pharmaceut Design 2003; 9: 2303-16.
19. Yoneda K, Iwamura R, Kishi H et al. Identification of the active metabolite of ticlopidine from rat in vitro metabolites. Br J Pharmacol 2004; 142: 551-7.
20. Reist M, Roy-de Vos M, Montseny JP et al. Very slow chiral inversion of clopidogrel in rats: a pharmacokinetic and mechanistic investigation. Drug Metab Dispos 2000; 28: 1405-10.
21. Pereillo JM, Maftouh M, Andrieu A et al. Structure and stereochemistry of the active metabolite of clopidogrel. Drug Metab Dispos 2002; 30: 1288-95.
22. 12, a new platelet ADP receptor, target of clopidogrel. Biochem Biophys Res Commun 2001; 283: 379-83.
23. 12 receptor by thiol reagents requires interaction with both extracellular cysteine residues, Cys17 and Cys270. Blood 2003; 101: 3908-14.
24. Copeland RA, Williams JM, Giannaras J et al. Mechanism of selective inhibition of the inducible isoform of prostaglandin G/H synthase. Proc Natl Acad Sci 1994; 91: 11202-6.
25. Kijima H, Isobe Y, Muramatsu M et al. Structure-activity characterization of an H2-receptor antagonist, 3-amino-4-[4-[4-(1-piperidinomethyl)-2-pyridyloxy]-cis-2-butenylaminol- 3-cyclobutene-1,2-dione hydrochloride (IT-066), involved in the insurmountable antagonism against histamine-induced positive chronotropic action in guinea pig atria. Biochem Pharmacol 1998; 55: 151-7.
26. Winkler JD, Sung CM, Chabot-Flecher M et al. β-lactams SB 212047 and SB 216754 are irreversible, time-dependent inhibitors of coenzyme A-independent transacylase. Mol Pharmacol 1998; 53: 322-9.