Antithrombotic phosphoinositide 3-kinase β inhibitors in humans: A 'shear' delight!

Journal of Thrombosis and Haemostasis

Volumn 10, Issue 10, 2012, Pages 2123-2126

  Jackson, S P ^a   Schoenwaelder, S M ^a  

^a MONASH UNIVERSITY   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

9 (1 ANILINOETHYL) 7 METHYL 2 MORPHOLINOPYRIDO[1,2 A]PYRIMIDIN 4 ONE; ACETYLSALICYLIC ACID; ANTITHROMBOCYTIC AGENT; AZD 6482; FIBRINOLYTIC AGENT; KN 309; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE ALPHA; PHOSPHATIDYLINOSITOL 3 KINASE BETA; PHOSPHATIDYLINOSITOL 3 KINASE BETA INHIBITOR; PHOSPHATIDYLINOSITOL 3 KINASE DELTA; PHOSPHATIDYLINOSITOL 3 KINASE GAMMA; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PURINERGIC P2Y RECEPTOR ANTAGONIST; PURINERGIC P2Y12 RECEPTOR ANTAGONIST; UNCLASSIFIED DRUG;

ACUTE CORONARY SYNDROME; ANTICOAGULANT THERAPY; BLEEDING; CEREBROVASCULAR ACCIDENT; DRUG BLOOD LEVEL; DRUG HALF LIFE; DRUG POTENCY; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; HUMAN; IC 50; NONHUMAN; NOTE; PERCUTANEOUS CORONARY INTERVENTION; PRIORITY JOURNAL; PROTEIN EXPRESSION; THROMBOCYTE AGGREGATION INHIBITION; THROMBOSIS; THROMBOSIS PREVENTION;

ANIMALS; BLOOD PLATELETS; CLASS IA PHOSPHATIDYLINOSITOL 3-KINASE; FIBRINOLYTIC AGENTS; HEMOSTATICS; HUMANS; INSULIN RESISTANCE; MALE; ORTHO-AMINOBENZOATES; PLATELET AGGREGATION INHIBITORS; PROTEIN KINASE INHIBITORS; PYRIMIDINONES;

EID: 84866874713     PISSN: 15387933     EISSN: 15387836     Source Type: Journal    
DOI: 10.1111/j.1538-7836.2012.04912.x     Document Type: Note

References (26)

1. Patrono C, Baigent C, Hirsh J, Roth G. Antiplatelet drugs: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133: 199S-233S.
2. Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr, Chavey WE 2nd, Fesmire FM, Hochman JS, Levin TN, Lincoff AM, Peterson ED, Theroux P, Wenger NK, Wright RS, Smith SC Jr, Jacobs AK, Halperin JL, Hunt SA, Krumholz HM, et al. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non ST-elevation myocardial infarction. Circulation 2007; 116: e148-304.
3. Kushner FG, Hand M, Smith SC Jr, King SB 3rd, Anderson JL, Antman EM, Bailey SR, Bates ER, Blankenship JC, Casey DE Jr, Green LA, Hochman JS, Jacobs AK, Krumholz HM, Morrison DA, Ornato JP, Pearle DL, Peterson ED, Sloan MA, Whitlow PL, et al. A2009 Focused Updates: ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction (updating the 2004 Guideline and 2007 Focused Update) and ACC/AHA/SCAI Guidelines on Percutaneous Coronary Intervention (updating the 2005 Guideline and 2007 Focused Update). Circulation 2009; 120: 2271-306.
4. Sorensen R, Hansen ML, Abildstrom SZ, Hvelplund A, Andersson C, Jorgensen C, Madsen JK, Hansen PR, Kober L, Torp-Pedersen C, Gislason GH. Risk of bleeding in patients with acute myocardial infarction treated with different combinations of aspirin, clopidogrel, and vitamin K antagonists in Denmark: a retrospective analysis of nationwide registry data. Lancet 2009; 374: 1967-74.
5. Sobieraj-Teague M, Gallus AS, Eikelboom JW. The risk of iatrogenic bleeding in acute coronary syndromes and long-term mortality. Curr Opin Cardiol 2008; 23: 327-34.
6. Molina CA, Saver JL. Extending reperfusion therapy for acute ischemic stroke: emerging pharmacological, mechanical, and imaging strategies. Stroke 2005; 36: 2311-20.
7. Nylander S, Kull B, Bjorkman J, Ulvinge J, Oakes N, Emanuelsson B, Skarby T, Andersson M, Inghardt T, Fjellstrom O, Gustafsson D. Human target validation of phosphoinositide 3-kinase (PI3K)β; effects on platelets and insulin sensitivity, using AZD6482 a novel PI3Kβ inhibitor. J Thromb Haemost 2012; 10: 2127-36.
8. Jackson SP, Schoenwaelder SM, Goncalves I, Nesbitt WS, Yap CL, Wright CE, Kenche V, Anderson KE, Dopheide SM, Yuan Y, Sturgeon SA, Prabaharan H, Thompson PE, Smith GD, Shepherd PR, Daniele N, Kulkarni S, Abbott B, Saylik D, Jones C, et al. PI 3-kinase p110beta: a new target for antithrombotic therapy. Nat Med 2005; 11: 507-14.
9. Liu P, Cheng H, Roberts TM, Zhao JJ. Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov 2009; 8: 627-44.
10. Fruman DA, Meyers RE, Cantley LC. Phosphoinositide kinases. Annu Rev Biochem 1998; 67: 481-507.
11. Gilio K, Munnix IC, Mangin P, Cosemans JM, Feijge MA, van der Meijden PE, Olieslagers S, Chrzanowska-Wodnicka MB, Lillian R, Schoenwaelder S, Koyasu S, Sage SO, Jackson SP, Heemskerk JW. Non-redundant roles of phosphoinositide 3-kinase isoforms α and β in glycoprotein VI-induced platelet signaling and thrombus formation. J Biol Chem 2009; 284: 33750-62.
12. 3. Curr Top Microbiol Immunol 2010; 346: 203-24.
13. Kim S, Mangin P, Dangelmaier C, Lillian R, Jackson SP, Daniel JL, Kunapuli SP. Role of phosphoinositide 3-kinase β in glycoprotein VI-mediated Akt activation in platelets. J Biol Chem 2009; 284: 33763-72.
14. 3 avidity and the cellular transmission of contractile forces. J Biol Chem 2010; 285: 2886-96.
15. 3 adhesive function in platelets. J Biol Chem 2007; 282: 28648-58.
16. 2+ mobilization and procoagulant activity. FEBS J 2008; 275: 371-85.
17. i signalling pathways. Biochem J 2010; 429: 369-77.
18. Canobbio I, Stefanini L, Cipolla L, Ciraolo E, Gruppi C, Balduini C, Hirsch E, Torti M. Genetic evidence for a predominant role of PI3Kβ catalytic activity in ITAM- and integrin-mediated signaling in platelets. Blood 2009; 114: 2193-6.
19. Martin V, Guillermet-Guibert J, Chicanne G, Cabou C, Jandrot-Perrus M, Plantavid M, Vanhaesebroeck B, Payrastre B, Gratacap MP. Deletion of the p110β isoform of phosphoinositide 3-kinase in platelets reveals its central role in Akt activation and thrombus formation in vitro and in vivo. Blood 2010; 115: 2008-13.
20. Jackson SP, Robertson AD, Kenche V, Thompson P, Prabaharan H, Anderson KE, Abbott B, Goncalves I, Nesbitt WS, Schoenwaelder S, Saylik D. Inhibition of phosphoinositide 3-kinase beta. In: Bureau WIPO-I, ed. World Intellectual Property Organization - International Bureau. US: Kinacia Pty Ltd, Victoria, Australia, 2004.
21. Weerasinghe A, Taylor KM. The platelet in cardiopulmonary bypass. Ann Thorac Surg 1998; 66: 2145-52.
22. Sreeram GM, Sharma AD, Slaughter TF. Platelet glycoprotein IIb/IIIa antagonists: perioperative implications. J Cardiothorac Vasc Anesth 2001; 15: 237-40.
23. Straub A, Wendel HP, Dietz K, Schiebold D, Peter K, Schoenwaelder SM, Ziemer G. Selective inhibition of the platelet phosphoinositide 3-kinase p110β as promising new strategy for platelet protection during extracorporeal circulation. Thromb Haemost 2008; 99: 609-15.
24. Krajewski S, Kurz J, Geisler T, Peter K, Wendel HP, Straub A. Combined blockade of ADP receptors and PI3-kinase p110β fully prevents platelet and leukocyte activation during hypothermic extracorporeal circulation. PLoS One 2012; 7: e38455.
25. Mandava P, Thiagarajan P, Kent TA. Glycoprotein IIb/IIIa antagonists in acute ischaemic stroke: current status and future directions. Drugs 2008; 68: 1019-28.
26. Hermann A, Dzialowski I, Koch R, Gahn G. Combined anti-platelet therapy with aspirin and clopidogrel: risk factor for thrombolysis-related intracerebral hemorrhage in acute ischemic stroke? J Neurol Sci 2009; 284: 155-7.