BF061, a novel antiplatelet and antithrombotic agent targeting P2Y 12 receptor and phosphodiesterase

Thrombosis and Haemostasis

Volumn 106, Issue 6, 2011, Pages 1203-1214

  Hu, Liang ^a   Fan, Zhichao ^b   Du, Hongguang ^c   Ni, Ran ^d   Zhang, Si ^a   Yin, Kanhua ^a   Ye, Jianqin ^a   Zhang, Yan ^a   Wei, Xunbin ^b   Zhang, Xiaohui ^e   Gross, Peter L ^d   Kunapuli, Satya P ^f   Ding, Zhongren ^a  

^a FUDAN UNIVERSITY   (China)

^b FUDAN UNIVERSITY   (China)

^c BEIJING UNIVERSITY OF CHEMICAL TECHNOLOGY   (China)

^d MCMASTER UNIVERSITY   (Canada)

^e INSTITUTE OF BIOCHEMISTRY AND CELL BIOLOGY   (China)

^f TEMPLE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Antiplatelet; Antithrombotic; BF061; P2Y 12; PDE inhibitor; Receptor antagonist

Indexed keywords

15 HYDROXY 11ALPHA,9ALPHA EPOXYMETHANOPROSTA 5,13 DIENOIC ACID; 2 ETHYLTHIO 6 PHENETHYLAMINOADENOSINE; ANTITHROMBOCYTIC AGENT; BF 061; CANGRELOR; CLOPIDOGREL; CYCLIC AMP; CYCLIC GMP; FERROUS CHLORIDE; PHOSPHODIESTERASE; PURINERGIC P2Y12 RECEPTOR; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTITHROMBOTIC ACTIVITY; ARTERY THROMBOSIS; ARTICLE; ATOMIC FORCE MICROSCOPY; BLOOD SAMPLING; CONTROLLED STUDY; DRUG ACTIVITY; DRUG EFFICACY; DRUG SAFETY; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TARGETING; ENZYME ACTIVITY; ENZYME INHIBITION; HUMAN; HUMAN CELL; LASER; MALE; MOUSE; NONHUMAN; PREVALENCE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; THROMBOCYTE ACTIVATION; THROMBOGENESIS; TREATMENT RESPONSE;

ADENOSINE; ADENOSINE MONOPHOSPHATE; ANIMALS; DISEASE MODELS, ANIMAL; DRUG SYNERGISM; ENZYME INHIBITORS; FIBRINOLYTIC AGENTS; HUMANS; MICE; MICE, INBRED BALB C; MICE, INBRED C57BL; PHOSPHORIC DIESTER HYDROLASES; PLATELET ACTIVATION; PLATELET AGGREGATION INHIBITORS; PURINERGIC P2Y RECEPTOR ANTAGONISTS; THROMBOSIS;

EID: 82555193847     PISSN: 03406245     EISSN: None     Source Type: Journal    
DOI: 10.1160/TH11-06-0400     Document Type: Article

References (31)

1. Michelson AD. P2Y12 antagonism: promises and challenges. Arterioscler Thromb Vasc Biol 2008; 28: 33-38.
2. Chen KY, Rha SW, Li YJ, et al. Triple versus dual antiplatelet therapy in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Circulation 2009; 119: 3207-3214.
3. Lee SW, Park SW, Kim YH, et al. A Randomized, Double-Blind, Multicenter Comparison Study of Triple Antiplatelet Therapy With Dual Antiplatelet Therapy to Reduce Restenosis After Drug-Eluting Stent Implantation in Long Coronary Lesions Results From the DECLARE-LONG II (Drug-Eluting Stenting Followed by Cilostazol Treatment Reduces Late Restenosis in Patients with Long Coronary Lesions) Trial. J Am Coll Cardiol 2011; 57: 1264-1270.
4. Suh JW, Lee SP, Park KW, et al. Multicenter randomized trial evaluating the efficacy of cilostazol on ischemic vascular complications after drug-eluting stent implantation for coronary heart disease: Results of the CILON-T (Influence of CILostazol- based triple antiplatelet therapy ON ischemic complication after drugeluting stenT implantation) trial. J Am Coll Cardiol 2011; 57: 280-289.
5. Lee SW, Park SW, Hong MK, et al. Triple versus dual antiplatelet therapy after coronary stenting: impact on stent thrombosis. J Am Coll Cardiol 2005; 46: 1833-1837.
6. Lee K, Kim JY, Yoo BS, et al. Cilostazol augments the inhibition of platelet aggregation in clopidogrel low-responders. J Thromb Haemost 2010; 8: 2577-2579.
7. Shankar H, Murugappan S, Kim S, et al. Role of G protein-gated inwardly rectifying potassium channels in P2Y12 receptor-mediated platelet functional responses. Blood 2004; 104: 1335-1343.
8. Ding Z, Bynagari YS, Mada SR, et al. Studies on the role of the extracellular cysteines and oligomeric structures of the P2Y receptor when interacting with antagonists. J Thromb Haemost 2009; 7: 232-234.
9. Zhang S, Hu L, Du H, et al. BF0801, a novel adenine derivative, inhibits platelet activation via phosphodiesterase inhibition and P2Y12 antagonism. Thromb Haemost 2010; 104: 845-857.
10. Berlot C. Expression and functional analysis of G protein alpha subunits in mammalian cells. Boca Raton: CRC Press; 1999.
11. Ma T, Zhu X. Interleukin-6 increases the levels of cyclic GMP and nitrite in rat hippocampal slices. Eur J Pharmacol 1997; 321: 343-347.
12. Spoto G, Whitehead E, Ferraro A, et al. A reverse-phase HPLC method for cAMP phosphodiesterase activity. Anal Biochem 1991; 196: 207-210.
13. Tang HF, Song YH, Chen JC, et al. Upregulation of phosphodiesterase-4 in the lung of allergic rats. Am J Respir Crit Care Med 2005; 171: 823-828.
14. Ding Z, Kim S, Kunapuli SP. Identification of a Potent Inverse Agonist at a Constitutively Active Mutant of Human P2Y12 Receptor. Mol Pharmacol 2006; 69: 338-345.
15. Horber JK, Miles MJ. Scanning probe evolution in biology. Science 2003; 302: 1002-1005.
16. Hinterdorfer P, Dufrene YF. Detection and localization of single molecular recognition events using atomic force microscopy. Nat Methods 2006; 3: 347-355.
17. Banno F, Chauhan AK, Kokame K, et al. The distal carboxyl-terminal domains of ADAMTS13 are required for regulation of in vivo thrombus formation. Blood 2009; 113: 5323-5329.
18. Chauhan AK, Motto DG, Lamb CB, et al. Systemic antithrombotic effects of ADAMTS13. J Exp Med 2006; 203: 767-776.
19. Frenette PS, Johnson RC, Hynes RO, et al. Platelets roll on stimulated endothelium in vivo: an interaction mediated by endothelial P-selectin. Proc Natl Acad Sci USA 1995; 92: 7450-7454.
20. Angelillo-Scherrer A, Burnier L, Flores N, et al. Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy. J Clin Invest 2005; 115: 237-246.
21. Stolla M, Stefanini L, Roden RC, et al. The kinetics of alphaIIbbeta3 activation determines the size and stability of thrombi in mice: implications for antiplatelet therapy. Blood 2011; 117: 1005-1013.
22. Paul BZ, Jin J, Kunapuli SP. Molecular mechanism of thromboxane A(2)-induced platelet aggregation. Essential role for p2t(ac) and alpha(2a) receptors. J Biol Chem 1999; 274: 29108-29114.
23. Zhao L, Bath P, Heptinstall S. Effects of combining three different antiplatelet agents on platelets and leukocytes in whole blood in vitro. Br J Pharmacol 2001; 134: 353-358.
24. Orlowski E, Chand R, Yip J, et al. A platelet tetraspanin superfamily member, CD151, is required for regulation of thrombus growth and stability in vivo. J Thromb Haemost 2009; 7: 2074-2084.
25. Lenain N, Freund M, Leon C, et al. Inhibition of localized thrombosis in P2Y1-deficient mice and rodents treated with MRS2179, a P2Y1 receptor antagonist. J Thromb Haemost 2003; 1: 1144-1149.
26. Hechler B, Nonne C, Roh EJ, et al. MRS2500 [2-Iodo-N6-methyl-(N)-methanocarba- 2'-deoxyadenosine-3',5'-bisphosphate], a Potent, Selective, and Stable Antagonist of the Platelet P2Y1 Receptor with Strong Antithrombotic Activity in Mice. J Pharmacol Exp Ther 2006; 316: 556-563.
27. Lee SW, Park SW, Yun SC, et al. Triple antiplatelet therapy reduces ischemic events after drug-eluting stent implantation: Drug-Eluting stenting followed by Cilostazol treatment REduces Adverse Serious cardiac Events (DECREASE registry). Am Heart J 2010; 159: 284-291.
28. Han Y, Li Y, Wang S, et al. Cilostazol in addition to aspirin and clopidogrel improves long-term outcomes after percutaneous coronary intervention in patients with acute coronary syndromes: a randomized, controlled study. Am Heart J 2009; 157: 733-739.
29. Andre P, Deguzman F, Haberstock-Debic H, et al. Thienopyridines, but Not Elinogrel, Result in Off-Target Effects at the Vessel Wall That Contribute to Bleeding. J Pharmacol Exp Ther 2011; epub ahead of print.
30. Sibbing D, Steinhubl SR, Schulz S, et al. Platelet aggregation and its association with stent thrombosis and bleeding in clopidogrel-treated patients: initial evidence of a therapeutic window. J Am Coll Cardiol 2010; 56: 317-318.
31. Ferreiro JL, Sibbing D, Angiolillo DJ. Platelet function testing and risk of bleeding complications. Thromb Haemost 2010; 103: 1128-1135.