factor xa

Summary

Summary: Activated form of factor X that participates in both the intrinsic and extrinsic pathways of blood coagulation. It catalyzes the conversion of prothrombin to thrombin in conjunction with other cofactors.

Top Publications

  1. ncbi The discovery and development of rivaroxaban, an oral, direct factor Xa inhibitor
    Elisabeth Perzborn
    Global Therapeutic Research, Pharma R and D, Bayer HealthCare, Wuppertal, Germany
    Nat Rev Drug Discov 10:61-75. 2011
  2. ncbi Clinical safety, tolerability, pharmacokinetics, and pharmacodynamics of the novel factor Xa inhibitor edoxaban in healthy volunteers
    Koichiro Ogata
    Daiichi Sankyo Co, Ltd Tokyo, Japan
    J Clin Pharmacol 50:743-53. 2010
  3. ncbi Evaluation of the anti-factor Xa chromogenic assay for the measurement of rivaroxaban plasma concentrations using calibrators and controls
    Meyer Michel Samama
    Hotel Dieu University Hospital, Paris, France
    Thromb Haemost 107:379-87. 2012
  4. pmc Effects of renal impairment on the pharmacokinetics, pharmacodynamics and safety of rivaroxaban, an oral, direct Factor Xa inhibitor
    Dagmar Kubitza
    Clinical Pharmacology, Bayer Schering Pharma AG, 42096 Wuppertal, Germany
    Br J Clin Pharmacol 70:703-12. 2010
  5. ncbi Apixaban versus enoxaparin for thromboprophylaxis after hip replacement
    Michael Rud Lassen
    Department of Orthopedics, Spine Clinic, and Clinical Trial Unit, Hørsholm Hospital, University of Copenhagen, Hørsholm, Denmark
    N Engl J Med 363:2487-98. 2010
  6. ncbi A critical review of the methods for cleavage of fusion proteins with thrombin and factor Xa
    Richard J Jenny
    Haematologic Technologies, Inc, Essex Junction, VT, USA
    Protein Expr Purif 31:1-11. 2003
  7. ncbi Safety, pharmacodynamics, and pharmacokinetics of single doses of BAY 59-7939, an oral, direct factor Xa inhibitor
    Dagmar Kubitza
    Bayer HealthCare AG, Institute of Clinical Pharmocology, D 42096 Wuppertal, Germany
    Clin Pharmacol Ther 78:412-21. 2005
  8. pmc Lufaxin, a novel factor Xa inhibitor from the salivary gland of the sand fly Lutzomyia longipalpis blocks protease-activated receptor 2 activation and inhibits inflammation and thrombosis in vivo
    Nicolas Collin
    Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20892, USA
    Arterioscler Thromb Vasc Biol 32:2185-98. 2012
  9. pmc Effect of hepatic impairment on the pharmacokinetics and pharmacodynamics of a single dose of rivaroxaban, an oral, direct Factor Xa inhibitor
    Dagmar Kubitza
    Clinical Pharmacology, Bayer Pharma AG, Wuppertal, Germany
    Br J Clin Pharmacol 76:89-98. 2013
  10. ncbi Novel oral factor Xa and thrombin inhibitors in the management of thromboembolism
    Bengt I Eriksson
    Department of Orthopaedics, Sahlgrenska University Hospital, Molndal, Sweden
    Annu Rev Med 62:41-57. 2011

Research Grants

Detail Information

Publications325 found, 100 shown here

  1. ncbi The discovery and development of rivaroxaban, an oral, direct factor Xa inhibitor
    Elisabeth Perzborn
    Global Therapeutic Research, Pharma R and D, Bayer HealthCare, Wuppertal, Germany
    Nat Rev Drug Discov 10:61-75. 2011
    The activated serine protease factor Xa is a promising target for new anticoagulants...
  2. ncbi Clinical safety, tolerability, pharmacokinetics, and pharmacodynamics of the novel factor Xa inhibitor edoxaban in healthy volunteers
    Koichiro Ogata
    Daiichi Sankyo Co, Ltd Tokyo, Japan
    J Clin Pharmacol 50:743-53. 2010
    ..PD) study of a single ascending dose (SAD) and a multiple ascending dose (MAD) of the oral direct factor Xa inhibitor edoxaban in healthy males...
  3. ncbi Evaluation of the anti-factor Xa chromogenic assay for the measurement of rivaroxaban plasma concentrations using calibrators and controls
    Meyer Michel Samama
    Hotel Dieu University Hospital, Paris, France
    Thromb Haemost 107:379-87. 2012
    Rivaroxaban is an oral, direct factor Xa inhibitor. Routine coagulation monitoring is not required, but a quantitative determination of rivaroxaban concentrations might be useful in some clinical circumstances...
  4. pmc Effects of renal impairment on the pharmacokinetics, pharmacodynamics and safety of rivaroxaban, an oral, direct Factor Xa inhibitor
    Dagmar Kubitza
    Clinical Pharmacology, Bayer Schering Pharma AG, 42096 Wuppertal, Germany
    Br J Clin Pharmacol 70:703-12. 2010
    This study evaluated the effects of impaired renal function on the pharmacokinetics, pharmacodynamics and safety of rivaroxaban (10mg single dose), an oral, direct Factor Xa inhibitor.
  5. ncbi Apixaban versus enoxaparin for thromboprophylaxis after hip replacement
    Michael Rud Lassen
    Department of Orthopedics, Spine Clinic, and Clinical Trial Unit, Hørsholm Hospital, University of Copenhagen, Hørsholm, Denmark
    N Engl J Med 363:2487-98. 2010
    ..Low-molecular-weight heparins such as enoxaparin predominantly inhibit factor Xa but also inhibit thrombin to some degree...
  6. ncbi A critical review of the methods for cleavage of fusion proteins with thrombin and factor Xa
    Richard J Jenny
    Haematologic Technologies, Inc, Essex Junction, VT, USA
    Protein Expr Purif 31:1-11. 2003
    ..Thrombin and factor Xa are the most frequently used proteases for this application...
  7. ncbi Safety, pharmacodynamics, and pharmacokinetics of single doses of BAY 59-7939, an oral, direct factor Xa inhibitor
    Dagmar Kubitza
    Bayer HealthCare AG, Institute of Clinical Pharmocology, D 42096 Wuppertal, Germany
    Clin Pharmacol Ther 78:412-21. 2005
    ..Given its integral role in the coagulation cascade, factor Xa is a particularly promising target for new anticoagulation therapies...
  8. pmc Lufaxin, a novel factor Xa inhibitor from the salivary gland of the sand fly Lutzomyia longipalpis blocks protease-activated receptor 2 activation and inhibits inflammation and thrombosis in vivo
    Nicolas Collin
    Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20892, USA
    Arterioscler Thromb Vasc Biol 32:2185-98. 2012
    ..The aim of the present study was to identify the unique salivary anticoagulant of the sand fly Lutzomyia longipalpis, which remained elusive for decades...
  9. pmc Effect of hepatic impairment on the pharmacokinetics and pharmacodynamics of a single dose of rivaroxaban, an oral, direct Factor Xa inhibitor
    Dagmar Kubitza
    Clinical Pharmacology, Bayer Pharma AG, Wuppertal, Germany
    Br J Clin Pharmacol 76:89-98. 2013
    This study investigated the effects of hepatic impairment on the pharmacokinetics and pharmacodynamics of a single dose of rivaroxaban (10 mg), an oral, direct Factor Xa inhibitor.
  10. ncbi Novel oral factor Xa and thrombin inhibitors in the management of thromboembolism
    Bengt I Eriksson
    Department of Orthopaedics, Sahlgrenska University Hospital, Molndal, Sweden
    Annu Rev Med 62:41-57. 2011
    ..Edoxaban, an oral FXa inhibitor, is also being evaluated in phase III clinical trials. This review summarizes the pharmacology, clinical trial results, and future role of the new oral anticoagulants in clinical practice...
  11. ncbi Guidance on the emergent reversal of oral thrombin and factor Xa inhibitors
    Scott Kaatz
    Department of Medicine, Henry Ford Hospital, Detroit, Michigan 48202, USA
    Am J Hematol 87:S141-5. 2012
    ..Also, the pros and cons of the possible use of four factor prothrombin complex concentrate are discussed...
  12. pmc Apixaban, an oral, direct factor Xa inhibitor: single dose safety, pharmacokinetics, pharmacodynamics and food effect in healthy subjects
    Charles Frost
    Discovery Medicine and Clinical Pharmacology, Bristol Myers Squibb, Princeton, NJ 08543 4000, USA
    Br J Clin Pharmacol 75:476-87. 2013
    ..To evaluate apixaban single dose safety, tolerability, pharmacokinetics and pharmacodynamics and assess the effect of food on apixaban pharmacokinetics...
  13. ncbi Apixaban or enoxaparin for thromboprophylaxis after knee replacement
    Michael Rud Lassen
    Department of Orthopedics, Spine Clinic, Clinical Trial Unit, Hørsholm Hospital, University of Copenhagen, Hørsholm, Denmark
    N Engl J Med 361:594-604. 2009
    ..Low-molecular-weight heparins such as enoxaparin predominantly target factor Xa but to some extent also inhibit thrombin...
  14. ncbi Safety of edoxaban, an oral factor Xa inhibitor, in Asian patients with non-valvular atrial fibrillation
    Namsik Chung
    Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
    Thromb Haemost 105:535-44. 2011
    Edoxaban is an oral, reversible, direct factor Xa inhibitor in phase III clinical development for the prevention of stroke in atrial fibrillation (AF)...
  15. pmc Alboserpin, a factor Xa inhibitor from the mosquito vector of yellow fever, binds heparin and membrane phospholipids and exhibits antithrombotic activity
    Eric Calvo
    Section of Vector Biology, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA
    J Biol Chem 286:27998-8010. 2011
    The molecular mechanism of factor Xa (FXa) inhibition by Alboserpin, the major salivary gland anticoagulant from the mosquito and yellow fever vector Aedes albopictus, has been characterized...
  16. ncbi Apixaban with antiplatelet therapy after acute coronary syndrome
    John H Alexander
    Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27715, USA
    N Engl J Med 365:699-708. 2011
    Apixaban, an oral, direct factor Xa inhibitor, may reduce the risk of recurrent ischemic events when added to antiplatelet therapy after an acute coronary syndrome.
  17. ncbi Chromogenic laboratory assays to measure the factor Xa-inhibiting properties of apixaban--an oral, direct and selective factor Xa inhibitor
    Richard C Becker
    Division of Cardiology, Duke University School of Medicine, Duke University Medical Center, Duke Clinical Research Institute, Advanced Biomarker Program, 2400 Pratt Street, Durham, NC 27705, USA
    J Thromb Thrombolysis 32:183-7. 2011
    An ability to readily determine an anticoagulant effect with an emerging class of direct, active site, oral factor Xa inhibitors is viewed by the medical community as attractive and by some as an absolute requirement for their use in ..
  18. ncbi A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa
    Genmin Lu
    Department of Biology, Portola Pharmaceuticals Inc, South San Francisco, California, USA
    Nat Med 19:446-51. 2013
    Inhibitors of coagulation factor Xa (fXa) have emerged as a new class of antithrombotics but lack effective antidotes for patients experiencing serious bleeding...
  19. ncbi A new Factor Xa inhibitor from Amblyomma cajennense with a unique domain composition
    I F C Batista
    Laboratorio de Bioquimica e Biofisica, Instituto Butantan, Av Vital Brasil, Sao Paulo, SP, Brazil
    Arch Biochem Biophys 493:151-6. 2010
    ..5kDa) was produced in Escherichia coli BL21 (DE3), and it was able to inhibit Factor Xa (FXa) and extend global blood clotting times in vitro and ex vivo...
  20. ncbi The influence of age and gender on the pharmacokinetics and pharmacodynamics of rivaroxaban--an oral, direct Factor Xa inhibitor
    Dagmar Kubitza
    Clinical Pharmacology, Bayer HealthCare AG, Wuppertal, Germany
    J Clin Pharmacol 53:249-55. 2013
    ..the effect of age and gender on the pharmacokinetics and pharmacodynamics of rivaroxaban - an oral, direct Factor Xa inhibitor...
  21. ncbi Management consensus guidance for the use of rivaroxaban--an oral, direct factor Xa inhibitor
    Alexander G G Turpie
    Department of Medicine, McMaster University, Hamilton, Ontario, Canada
    Thromb Haemost 108:876-86. 2012
    A number of novel oral anticoagulants that directly target factor Xa or thrombin have been developed in recent years...
  22. ncbi Pharmacokinetics, biotransformation, and mass balance of edoxaban, a selective, direct factor Xa inhibitor, in humans
    Mohinder S Bathala
    Daiichi Sankyo Pharma Development, Edison, New Jersey, USA
    Drug Metab Dispos 40:2250-5. 2012
    ..Edoxaban is eliminated through multiple pathways, but each accounts for only a small amount of overall elimination...
  23. ncbi Randomised, parallel-group, multicentre, multinational phase 2 study comparing edoxaban, an oral factor Xa inhibitor, with warfarin for stroke prevention in patients with atrial fibrillation
    Jeffrey I Weitz
    Thrombosis and Atherosclerosis Research Institute, Hamilton General Hospital, Ontario, Canada
    Thromb Haemost 104:633-41. 2010
    ..In contrast, the edoxaban bid regimens were associated with more bleeding than warfarin. These results suggest that in this three-month study, edoxaban 30 or 60 mg qd are safe and well-tolerated...
  24. ncbi Assessment of laboratory assays to measure rivaroxaban--an oral, direct factor Xa inhibitor
    Meyer Michel Samama
    Hotel Dieu University Hospital, Paris, France 2Biomnis Laboratory, Ivry sur Seine, France
    Thromb Haemost 103:815-25. 2010
    Although there is no need for routine coagulation monitoring with rivaroxaban--an oral, direct factor Xa inhibitor--a haemostasis assay might be valuable to measure its pharmacodynamic effects...
  25. ncbi Efficacy and safety of the oral direct factor Xa inhibitor apixaban for symptomatic deep vein thrombosis. The Botticelli DVT dose-ranging study
    H Buller
    Department of Vascular Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
    J Thromb Haemost 6:1313-8. 2008
    ..We conducted a dose-ranging study in patients with deep vein thrombosis...
  26. ncbi Apixaban, an oral, direct and highly selective factor Xa inhibitor: in vitro, antithrombotic and antihemostatic studies
    P C Wong
    Thrombosis Research, Bristol Myers Squibb Company, Pennington, NJ 08534, USA
    J Thromb Haemost 6:820-9. 2008
    Apixaban is an oral, direct and highly selective factor Xa (FXa) inhibitor in late-stage clinical development for the prevention and treatment of thromboembolic diseases.
  27. ncbi In vitro and in vivo studies of the novel antithrombotic agent BAY 59-7939--an oral, direct Factor Xa inhibitor
    E Perzborn
    Cardiovascular Research, Bayer HealthCare AG, Wuppertal, Germany
    J Thromb Haemost 3:514-21. 2005
    BAY 59-7939 is an oral, direct Factor Xa (FXa) inhibitor in development for the prevention and treatment of arterial and venous thrombosis. BAY 59-7939 competitively inhibits human FXa (K(i) 0...
  28. ncbi Evaluation of the novel factor Xa inhibitor edoxaban compared with warfarin in patients with atrial fibrillation: design and rationale for the Effective aNticoaGulation with factor xA next GEneration in Atrial Fibrillation-Thrombolysis In Myocardial Infar
    Christian T Ruff
    TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    Am Heart J 160:635-41. 2010
    ..Edoxaban is a selective and direct factor Xa inhibitor that may provide effective, safe, and more convenient anticoagulation.
  29. ncbi Clinical laboratory measurement of direct factor Xa inhibitors: anti-Xa assay is preferable to prothrombin time assay
    Yu Chen Barrett
    Bristol Myers Squibb, Princeton, New Jersey, USA
    Thromb Haemost 104:1263-71. 2010
    Apixaban and other factor Xa (FXa) inhibitors are in late-stage clinical development for prevention and treatment of thromboembolic diseases...
  30. ncbi Population pharmacokinetics and pharmacodynamics of rivaroxaban--an oral, direct factor Xa inhibitor--in patients undergoing major orthopaedic surgery
    Wolfgang Mueck
    Clinical Pharmacology, Bayer HealthCare AG, Aprather Weg 18a, Wuppertal, Germany
    Clin Pharmacokinet 47:203-16. 2008
    ..Rivaroxaban is an oral direct Factor Xa (FXa) inhibitor in clinical development for the prevention and treatment of thromboembolic disorders...
  31. pmc Role of the active-site solvent in the thermodynamics of factor Xa ligand binding
    Robert Abel
    Department of Chemistry, Columbia University, 3000 Broadway, New York, New York 10027, USA
    J Am Chem Soc 130:2817-31. 2008
    ..81) the binding free energy differences between congeneric ligand pairs for the test system factor Xa, elucidates physical properties of the active-site solvent that appear to be missing in most continuum theories ..
  32. ncbi Effects of food on the pharmacokinetics of edoxaban, an oral direct factor Xa inhibitor, in healthy volunteers
    Jeanne Mendell
    MPH, Daiichi Sankyo Pharma Development, 399 Thornall St, Edison, NJ 08837, USA
    J Clin Pharmacol 51:687-94. 2011
    ..Both Japanese and Caucasian volunteers demonstrated a modest but clinically insignificant food effect. It was concluded that edoxaban can be administered without regard to food...
  33. ncbi In vitro metabolism of rivaroxaban, an oral, direct factor Xa inhibitor, in liver microsomes and hepatocytes of rats, dogs, and humans
    D Lang
    Bayer HealthCare AG, Global Drug Discovery, DMPK Drug Metabolism, Building 466, Aprather Weg 18a, D 42096 Wuppertal, Germany
    Drug Metab Dispos 37:1046-55. 2009
    The in vitro metabolism of rivaroxaban, a novel, oral, direct factor Xa inhibitor for the prevention and treatment of thromboembolic disorders, was investigated in several species, including humans...
  34. pmc Safety, pharmacokinetics and pharmacodynamics of multiple oral doses of apixaban, a factor Xa inhibitor, in healthy subjects
    Charles Frost
    Bristol Myers Squibb, Princeton, NJ, USA
    Br J Clin Pharmacol 76:776-86. 2013
    Apixaban is an oral factor Xa inhibitor approved for stroke prevention in atrial fibrillation and thromboprophylaxis in patients who have undergone elective hip or knee replacement surgery and under development for treatment of venous ..
  35. ncbi In vitro assessment of metabolic drug-drug interaction potential of apixaban through cytochrome P450 phenotyping, inhibition, and induction studies
    Lifei Wang
    Pharmaceutical Candidate Optimization, Bristol Myers Squibb Research and Development, Princeton, New Jersey 08543, USA
    Drug Metab Dispos 38:448-58. 2010
    Apixaban is an oral, direct, and highly selective factor Xa inhibitor in late-stage clinical development for the prevention and treatment of thromboembolic diseases...
  36. pmc Preclinical discovery of apixaban, a direct and orally bioavailable factor Xa inhibitor
    Pancras C Wong
    Department of Cardiovascular Biology, Bristol Myers Squibb Company, 311 Pennington Rocky Hill Road, Pennington, NJ 08534, USA
    J Thromb Thrombolysis 31:478-92. 2011
    ..Together, these non-clinical findings have established the favorable pharmacological profile of apixaban, and support the potential use of apixaban in the clinic for the prevention and treatment of various thromboembolic diseases...
  37. ncbi Preclinical pharmacokinetics and pharmacodynamics of apixaban, a potent and selective factor Xa inhibitor
    Kan He
    Pharmaceutical Candidate Optimization, Bristol Myers Squibb Company, Princeton, NJ, USA
    Eur J Drug Metab Pharmacokinet 36:129-39. 2011
    Apixaban is a potent, highly selective, reversible, oral, direct factor Xa (fXa) inhibitor in development for thrombosis prevention and treatment...
  38. ncbi Factor Xa subsite mapping by proteome-derived peptide libraries improved using WebPICS, a resource for proteomic identification of cleavage sites
    Oliver Schilling
    Institute for Molecular Medicine and Cell Research, University of Freiburg, Germany
    Biol Chem 392:1031-7. 2011
    ..We demonstrate the utility of WebPics analysis of PICS data by determining the substrate specificity of factor Xa from P6-P6', an important blood coagulation protease that proteolytically generates thrombin from prothrombin...
  39. ncbi Effects of the oral, direct factor xa inhibitor rivaroxaban on platelet-induced thrombin generation and prothrombinase activity
    Jochen Graff
    Pharmazentrum frankfurt ZAFES, Institute of Clinical Pharmacology, University Hospital, Frankfurt Main, Theodor Stern Kai 7, D 60590 Frankfurt am Main, Germany
    J Clin Pharmacol 47:1398-407. 2007
    Rivaroxaban (BAY 59-7939) is an oral, direct factor Xa inhibitor in advanced development. This study was undertaken to investigate its effects on thrombin generation...
  40. pmc Isolation of a protein Z-dependent plasma protease inhibitor
    X Han
    Division of Hematology, Barnes Jewish Hospital at Washington University School of Medicine, 216 South Kingshighway Boulevard, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 95:9250-5. 1998
    ..The procoagulant activity of factor Xa in a one-stage plasma coagulation assay is reduced when factor Xa is first incubated with PZ...
  41. ncbi Structure-function relationships and mechanism of anticoagulant phospholipase A2 enzymes from snake venoms
    R Manjunatha Kini
    Protein Science Laboratory, Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore
    Toxicon 45:1147-61. 2005
    ..CM-IV binds to factor Xa and interferes in its interaction with factor Va and the formation of prothrombinase complex...
  42. pmc Antithrombin-S195A factor Xa-heparin structure reveals the allosteric mechanism of antithrombin activation
    Daniel J D Johnson
    Department of Haematology, Division of Stuctural Medicine, Thrombosis Research Unit, Cambridge Institute for Medical Research, University of Cambridge, UK
    EMBO J 25:2029-37. 2006
    ..This structure explains the molecular basis of protease recognition by AT, and the mechanism of action of the important therapeutic low-molecular-weight heparins...
  43. ncbi Oral, direct Factor Xa inhibition with BAY 59-7939 for the prevention of venous thromboembolism after total hip replacement
    B I Eriksson
    Sahlgrenska University HospitalOstra, Gothenburg, Sweden
    J Thromb Haemost 4:121-8. 2006
    ..Joint replacement surgery is an appropriate model for dose-ranging studies investigating new anticoagulants...
  44. ncbi Specificity of coagulation factor signaling
    W Ruf
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Thromb Haemost 1:1495-503. 2003
    ..Protease receptors are thus major determinants of the biological outcome of coagulation factor signaling on vascular cells...
  45. ncbi Rationale and design of the Anti-Xa therapy to lower cardiovascular events in addition to standard therapy in subjects with acute coronary syndrome-thrombolysis in myocardial infarction 51 (ATLAS-ACS 2 TIMI 51) trial: a randomized, double-blind, placebo-c
    C Michael Gibson
    TIMI Study Group, Brigham and Women s Hospital, Boston, MA, USA
    Am Heart J 161:815-821.e6. 2011
    ..In a phase 2 trial (ClinicalTrials.gov NCT00402597) in which the addition of the factor Xa inhibitor rivaroxaban was compared with placebo, among ACS patients receiving either aspirin alone or dual-..
  46. ncbi DU-176b, a potent and orally active factor Xa inhibitor: in vitro and in vivo pharmacological profiles
    T Furugohri
    Biological Research Laboratories I, R and D Division, Daiichi Sankyo Co, Ltd, Shinagawa ku, Toyo, Japan
    J Thromb Haemost 6:1542-9. 2008
    b>Factor Xa (FXa), a key serine protease that converts prothrombin to thrombin in the coagulation cascade, is a promising target enzyme for the prophylaxis and treatment of thromboembolic diseases...
  47. ncbi Effect of food, an antacid, and the H2 antagonist ranitidine on the absorption of BAY 59-7939 (rivaroxaban), an oral, direct factor Xa inhibitor, in healthy subjects
    Dagmar Kubitza
    Institute of Clinical Pharmacology, Bayer HealthCare AG, Wuppertal, Germany
    J Clin Pharmacol 46:549-58. 2006
    ..Time to maximum PT prolongation was delayed by 0.5 to 1.5 hours after food, with no relevant influence of food type. No significant difference in C(max) and AUC was observed with coadministration of BAY 59-7939 and ranitidine or antacid...
  48. ncbi Apixaban for reduction in stroke and other ThromboemboLic events in atrial fibrillation (ARISTOTLE) trial: design and rationale
    Renato D Lopes
    Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA
    Am Heart J 159:331-9. 2010
    ..The primary objective of ARISTOTLE is to determine if the factor Xa inhibitor, apixaban, is noninferior to warfarin at reducing the combined endpoint of stroke (ischemic or ..
  49. ncbi Discovery of 1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide (apixaban, BMS-562247), a highly potent, selective, efficacious, and orally bioavailable inhibitor of blood coagulation fa
    Donald J P Pinto
    Discovery Chemistry, Research and Development, Bristol Myers Squibb Company, 31 Pennington Rocky Hill Road, Pennington, New Jersey 08534, USA
    J Med Chem 50:5339-56. 2007
    ..of the neutral P1 moieties that resulted in the identification of the p-methoxyphenyl P1, which retained factor Xa binding affinity and good oral bioavailability...
  50. ncbi Population model of the pharmacokinetics and pharmacodynamics of rivaroxaban--an oral, direct factor xa inhibitor--in healthy subjects
    W Mueck
    Clinical Pharmacology, Pharmacometry, Bayer HealthCare AG, Wuppertal, Germany
    Int J Clin Pharmacol Ther 45:335-44. 2007
    Rivaroxaban (BAY 59-7939) is an oral, direct Factor Xa (FXa) inhibitor being developed for the prevention and treatment of thromboembolic disorders...
  51. ncbi Apixaban, an oral, direct, selective factor Xa inhibitor, in combination with antiplatelet therapy after acute coronary syndrome: results of the Apixaban for Prevention of Acute Ischemic and Safety Events (APPRAISE) trial
    John H Alexander
    Duke Clinical Research Institute, Duke University Medical Center, DUMC Box 3850, Durham, NC 27715, USA
    Circulation 119:2877-85. 2009
    After an acute coronary syndrome, patients remain at risk of recurrent events. Apixaban, an oral direct factor Xa inhibitor, is a novel anticoagulant that may reduce these events but also poses a risk of bleeding.
  52. ncbi Discovery of the novel antithrombotic agent 5-chloro-N-({(5S)-2-oxo-3- [4-(3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)thiophene- 2-carboxamide (BAY 59-7939): an oral, direct factor Xa inhibitor
    Susanne Roehrig
    Bayer HealthCare AG, D 42096 Wuppertal, Germany
    J Med Chem 48:5900-8. 2005
    ..The coagulation enzyme Factor Xa (FXa) is a particularly promising target, and recent efforts in this field have focused on the identification of ..
  53. pmc Heparin is a major activator of the anticoagulant serpin, protein Z-dependent protease inhibitor
    Xin Huang
    Center for Molecular Biology of Oral Diseases, University of Illinois, Chicago, Illinois 60612, USA
    J Biol Chem 286:8740-51. 2011
    ..Heparin produced 20-100-fold accelerations of ZPI reactions with factor Xa and factor XIa to yield second order rate constants approaching the physiologically significant diffusion limit (..
  54. pmc Coagulation factor Xa cleaves protease-activated receptor-1 and mediates signaling dependent on binding to the endothelial protein C receptor
    R A Schuepbach
    Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Thromb Haemost 8:379-88. 2010
    ..Endothelial protein C receptor (EPCR) supports PAR1 signaling by the protein C pathway, and in the present study we tested whether EPCR mediates surface recruitment and signaling of FXa...
  55. pmc Determination of rivaroxaban by different factor Xa specific chromogenic substrate assays: reduction of interassay variability
    Job Harenberg
    Department of Clinical Pharmacology, University Heidelberg, Maybachstrasse 14, Mannheim, Germany
    J Thromb Thrombolysis 32:267-71. 2011
    Rivaroxaban and other oral direct factor Xa inhibitors (ODiXa) are currently developed for prophylaxis and treatment of thromboembolic diseases using fixed doses...
  56. ncbi The role of structural information in the discovery of direct thrombin and factor Xa inhibitors
    Herbert Nar
    Structural Research Group, Department of Lead Identification and Optimization Support, Boehringer Ingelheim Pharma GmbH and Co KG, Birkendorferstrasse 65, 88397 Biberach an der Riss, Germany
    Trends Pharmacol Sci 33:279-88. 2012
    ..Structure-guided design of inhibitors of thrombin (factor IIa, fIIa) and factor Xa (fXa) eventually led to the discovery of potent, selective, efficacious, orally active and safe compounds that ..
  57. ncbi Characterization of the protein Z-dependent protease inhibitor
    X Han
    Division of Hematology, Barnes Jewish Hospital at Washington University Medical Center, St Louis, MO 63110, USA
    Blood 96:3049-55. 2000
    ..ZPI) is a 72-kd member of the serpin superfamily of proteinase inhibitors that produces rapid inhibition of factor Xa in the presence of protein Z (PZ), procoagulant phospholipids, and Ca(++) (t(1/2) less than 10 seconds)...
  58. ncbi Roles of coagulation pathway and factor Xa in the progression of diabetic nephropathy in db/db mice
    Ayaka Sumi
    Department of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Japan
    Biol Pharm Bull 34:824-30. 2011
    The active type of coagulation factor X (factor Xa) activates various cell-types through protease-activated receptor 2 (PAR2). We previously reported that a factor Xa inhibitor could suppress Thy-1 nephritis...
  59. ncbi Safety and efficacy of the oral direct factor xa inhibitor apixaban in Japanese patients with non-valvular atrial fibrillation. -The ARISTOTLE-J study-
    Satoshi Ogawa
    International University of Health and Welfare, Mita Hospital, Japan
    Circ J 75:1852-9. 2011
    ..This phase II study assessed the effects of 2 doses of the factor Xa inhibitor apixaban vs. warfarin in Japanese patients with non-valvular AF...
  60. ncbi Edoxaban: a new oral direct factor xa inhibitor
    A John Camm
    Division of Clinical Sciences, St Georges University of London, UK
    Drugs 71:1503-26. 2011
    Edoxaban is an oral direct factor Xa inhibitor that is currently undergoing investigation in phase III clinical trials for the prevention of stroke in patients with atrial fibrillation (AF) and for the prevention and treatment of venous ..
  61. ncbi Edoxaban administration following enoxaparin: a pharmacodynamic, pharmacokinetic, and tolerability assessment in human subjects
    Hamim Zahir
    Daiichi Sankyo Pharma Development, 399 Thornall Street, Edison, NJ 08837, USA
    Thromb Haemost 108:166-75. 2012
    ..There were no serious adverse events during the study. It is concluded that a 60-mg dose of edoxaban can be safely administered 12 h following enoxaparin 1 mg/kg...
  62. ncbi A dose-ranging study evaluating the oral factor Xa inhibitor edoxaban for the prevention of venous thromboembolism in patients undergoing total knee arthroplasty
    T Fuji
    Osaka Koseinenkin Hospital, Osaka, Japan
    J Thromb Haemost 8:2458-68. 2010
    ..Edoxaban (the free base of DU-176b) is an oral, direct factor (F)Xa inhibitor in clinical development for the prevention and treatment of thromboembolic events...
  63. ncbi Absence of clinically relevant interactions between rivaroxaban--an oral, direct Factor Xa inhibitor--and digoxin or atorvastatin in healthy subjects
    D Kubitza
    Clinical Pharmacology, Bayer Pharma AG, Wuppertal, Germany
    J Int Med Res 40:1688-707. 2012
    To investigate potential interactions between rivaroxaban, an oral direct Factor Xa inhibitor approved for the management of thromboembolic disorders, and digoxin or atorvastatin.
  64. pmc Holothurian glycosaminoglycan inhibits metastasis and thrombosis via targeting of nuclear factor-κB/tissue factor/Factor Xa pathway in melanoma B16F10 cells
    Yang Zhao
    Department of Clinical Pharmacy, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, People s Republic of China
    PLoS ONE 8:e56557. 2013
    ..in B16F10 cells remarkably inhibited the formation of fibrin through attenuating the generation of activated Factor Xa (FXa), without affecting the expression of urokinase (uPA) and plasminogen activator inhibitor 1 (PAI-1) that ..
  65. ncbi Inhibition of the generation of thrombin and factor Xa by a fucoidan from the brown seaweed Ecklonia kurome
    T Nishino
    Department of Biosciences, School of Science, Kitasato University, Sagamihara, Kanagawa, Japan
    Thromb Res 96:37-49. 1999
    ..a fucoidan (C-II), which was purified from the brown seaweed Ecklonia kurome, on the generation of thrombin and factor Xa have been investigated by measuring the amidolytic activities by using the respective specific chromogenic ..
  66. ncbi Anticoagulant therapy with the oral direct factor Xa inhibitors rivaroxaban, apixaban and edoxaban and the thrombin inhibitor dabigatran etexilate in patients with hepatic impairment
    Jochen Graff
    Pharmazentrum frankfurt ZAFES, Institute of Clinical Pharmacology, Johann Wolfgang Goethe University, Theodor Stern Kai 7, 60590 Frankfurt, Germany
    Clin Pharmacokinet 52:243-54. 2013
    The direct factor Xa (FXa) inhibitors rivaroxaban, apixaban and edoxaban, and the thrombin inhibitor dabigatran etexilate (dabigatran) have gained approval for use in several indications, most notably for the prevention and treatment of ..
  67. ncbi Heparin-induced substrate behavior of antithrombin Cambridge II
    Alec Mushunje
    Department of Haematology, Cambridge Institute for Medical Research, Wellcome Trust MRC Building, Hills Road, Cambridge CB2 2XY, United Kingdom
    Blood 102:4028-34. 2003
    ..found to be normal in its affinity for heparin, its ability to form sodium dodecyl sulfate-stable complexes with factor Xa and thrombin, and its uncatalyzed stoichiometries and rates of inhibition...
  68. ncbi The pharmacokinetics of idraparinux, a long-acting indirect factor Xa inhibitor: population pharmacokinetic analysis from Phase III clinical trials
    C Veyrat-Follet
    Sanofi Aventis, Global Metabolism and Pharmacokinetics, Vitry sur Seine, Cedex, France
    J Thromb Haemost 7:559-65. 2009
    ..Idraparinux, a long-acting synthetic pentasaccharide, is a specific antithrombin-dependent inhibitor of activated factor X that has been investigated in the treatment and prevention of thromboembolic events...
  69. pmc L-asparaginase-induced antithrombin type I deficiency: implications for conformational diseases
    David Hernandez-Espinosa
    Centro Regional de Hemodonacion, Universidad de Murcia, Murcia 30003, Spain
    Am J Pathol 169:142-53. 2006
    ..l-Asparaginase treatment induces severe, acquired, and transient type I deficiency of antithrombin (and alpha1-antitrypsin) with intracellular accumulation of the nascent molecule, increasing the risk of thrombosis...
  70. ncbi New oral anticoagulants in development
    Jeffrey I Weitz
    Department of Medicine, McMaster University and Henderson Research Centre, Hamilton, Ontario, Canada
    Thromb Haemost 103:62-70. 2010
    ..These limitations have prompted the development of new oral anticoagulants that target thrombin or factor Xa and can be given in fixed doses without coagulation monitoring...
  71. ncbi Dosage of enoxaparin among obese and renal impairment patients
    Annie Bazinet
    Cité de la Santé de Laval, Quebec, Canada
    Thromb Res 116:41-50. 2005
    ..Enoxaparin dosage for obese patients and patients with renal impairment remains controversial...
  72. ncbi No correlation between anti-factor Xa levels, low-molecular-weight heparin, and bleeding after gastric bypass
    John T Paige
    Weight Management Center, Vista Surgical Hospital, Baton Rouge, Louisiana, USA
    Surg Obes Relat Dis 3:469-75. 2007
    ..Anti-factor Xa (AFXa) has been suggested as a potential marker of LMWH activity...
  73. pmc Anti-factor Xa kinetics after intravenous enoxaparin in patients undergoing percutaneous coronary intervention: a population model analysis
    Paola Sanchez-Pena
    Pharmacology Department, Pitie Salpetriere University Hospital, Assistance Publique Hospitaux de Paris, Paris 6 University, Paris, France
    Br J Clin Pharmacol 60:364-73. 2005
    ..v.) enoxaparin could be used as antithrombotic therapy in patients ongoing percutaneous coronary intervention (PCI). However, anti-Xa pharmacokinetics following different i.v. dosing regimens is not clearly established...
  74. pmc RUBY-1: a randomized, double-blind, placebo-controlled trial of the safety and tolerability of the novel oral factor Xa inhibitor darexaban (YM150) following acute coronary syndrome
    Ph Gabriel Steg
    INSERM U 698, Paris, France
    Eur Heart J 32:2541-54. 2011
    To establish the safety, tolerability and most promising regimen of darexaban (YM150), a novel, oral, direct factor Xa inhibitor, for prevention of ischaemic events in acute coronary syndrome (ACS).
  75. pmc Simukunin from the salivary glands of the black fly Simulium vittatum inhibits enzymes that regulate clotting and inflammatory responses
    Hitoshi Tsujimoto
    Department of Entomology, The University of Georgia, Athens, Georgia, United States of America
    PLoS ONE 7:e29964. 2012
    ..Blood feeding depends on pharmacological properties of saliva, including anticoagulation, but the molecules responsible for this activity have not been well characterized...
  76. ncbi Active and exo-site inhibition of human factor Xa: structure of des-Gla factor Xa inhibited by NAP5, a potent nematode anticoagulant protein from Ancylostoma caninum
    Jorge L Rios-Steiner
    Department of Chemistry, Michigan State University, East Lansing, MI 48824 1322, USA
    J Mol Biol 371:774-86. 2007
    ..One of these nematode anticoagulant proteins, NAP5, inhibits the amidolytic activity of factor Xa (fXa) with K(i)=43 pM, and is the most potent natural fXa inhibitor identified thus far...
  77. ncbi Genetic evidence that protease-activated receptors mediate factor Xa signaling in endothelial cells
    Eric Camerer
    Cardiovascular Research Institute, University of California, San Francisco, California 94143, USA
    J Biol Chem 277:16081-7. 2002
    The coagulation protease Factor Xa (Xa)(1) triggers a variety of cellular responses that may be important for inflammatory reactions to tissue injury...
  78. pmc Anticoagulation by factor Xa inhibitors
    T Orfeo
    Department of Biochemistry, University of Vermont, Colchester, VT, USA
    J Thromb Haemost 8:1745-53. 2010
    ..Therapeutic agents that regulate blood coagulation are critical to the management of thrombotic disorders, with the selective targeting of factor (F) Xa emerging as a promising approach...
  79. ncbi Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty
    Bengt I Eriksson
    Sahlgrenska University Hospital Ostra, Gothenburg, Sweden
    N Engl J Med 358:2765-75. 2008
    This phase 3 trial compared the efficacy and safety of rivaroxaban, an oral direct inhibitor of factor Xa, with those of enoxaparin for extended thromboprophylaxis in patients undergoing total hip arthroplasty.
  80. ncbi Interlaboratory agreement in the monitoring of unfractionated heparin using the anti-factor Xa-correlated activated partial thromboplastin time
    A Cuker
    Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA
    J Thromb Haemost 7:80-6. 2009
    ..APTT) be defined in each laboratory through correlation with a direct measure of heparin activity such as the factor Xa inhibition assay...
  81. ncbi Clinical pharmacology of direct and indirect factor Xa inhibitors
    Hans Juergen Rupprecht
    GPR Klinikum Ruesselsheim, Ruesselsheim, Germany
    Drugs 70:2153-70. 2010
    ..The central position of factor Xa (FXa) at the junction of the intrinsic and extrinsic pathways in the coagulation cascade means that direct and ..
  82. ncbi Structure- and property-based design of factor Xa inhibitors: pyrrolidin-2-ones with acyclic alanyl amides as P4 motifs
    Robert J Young
    GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK
    Bioorg Med Chem Lett 16:5953-7. 2006
    ..drug design was exploited in the synthesis of 3-(6-chloronaphth-2-ylsulfonyl)aminopyrrolidin-2-one-based factor Xa (fXa) inhibitors, incorporating an alanylamide P4 group with acyclic tertiary amide termini...
  83. ncbi Perspectives on factor Xa inhibition
    R Rai
    Axys Pharmaceuticals, Inc, 180 Kimball Way, South San Francisco, CA 94080, USA
    Curr Med Chem 8:101-19. 2001
    ..This cascade is comprised of two arms, the intrinsic and extrinsic pathways which converge at factor Xa to form the common pathway...
  84. doi Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomised, open-label, non-inferiority trial
    M G Bousser
    Lancet 371:315-21. 2008
    ..The aim of this randomised, open-label non-inferiority trial was to compare the efficacy and safety of idraparinux with vitamin K antagonists...
  85. pmc Anticoagulant activity of a sulfated galactan: serpin-independent effect and specific interaction with factor Xa
    Bianca F Glauser
    Laboratório de Tecido Conjuntivo, Hospital Universitario Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Cidade Universitaria, Ilha do Fundao, Rio de Janeiro, Brazil
    Thromb Haemost 102:1183-93. 2009
    ..In conclusion, sulfated galactan and heparin have some similar effects on blood coagulation, but also differ significantly at the molecular level. This sulfated galactan opens new perspective for the development of antithrombotic drugs...
  86. ncbi The significance of circulating factor IXa in blood
    Saulius Butenas
    Department of Biochemistry, University of Vermont, Burlington, Vermont 05405 0068, USA
    J Biol Chem 279:22875-82. 2004
    ..and select coagulation inhibitors at mean physiological concentrations, concentrations of factor IXa, factor Xa, and thrombin were set either equal to those of their AP or to values that would result based upon the rates of ..
  87. pmc Synergistic induction of tissue factor by coagulation factor Xa and TNF: evidence for involvement of negative regulatory signaling cascades
    Ayala Hezi-Yamit
    Millennium Pharmaceuticals, Inc, South San Francisco, CA 94080, USA
    Proc Natl Acad Sci U S A 102:12077-82. 2005
    ..In this report, we demonstrate synergistic interactions between the coagulation factor Xa (fXa) and the proinflammatory cytokines TNF, IL-1beta, and CD40L, leading to enhanced expression of TF and E-..
  88. ncbi Rivaroxaban: a new oral factor Xa inhibitor
    Elisabeth Perzborn
    Cardiovascular Pharmacology, Pharma R and D Discovery Research, Bayer Schering Pharma AG, Aprather Weg 18a, D 42096 Wuppertal, Germany
    Arterioscler Thromb Vasc Biol 30:376-81. 2010
    Rivaroxaban is a direct inhibitor of factor Xa, a coagulation factor at a critical juncture in the blood coagulation pathway leading to thrombin generation and clot formation...
  89. ncbi Inhibition of restenosis by tissue factor pathway inhibitor: in vivo and in vitro evidence for suppressed monocyte chemoattraction and reduced gelatinolytic activity
    Christoph W Kopp
    2nd Department of Medicine, Division of Angiology, University of Vienna Medical School, Vienna, Austria
    Blood 103:1653-61. 2004
    ..These results suggest that TFPI exerts its action in vivo through not only thrombotic, but also nonthrombotic mechanisms...
  90. ncbi Nonpeptide factor Xa inhibitors: I. Studies with SF303 and SK549, a new class of potent antithrombotics
    P C Wong
    Cardiovascular Diseases Research, DuPont Pharmaceuticals Company, Wilmington, DE 19880 0400, USA
    J Pharmacol Exp Ther 292:351-7. 2000
    A series of benzamidine isoxazoline derivatives was evaluated for their inhibitory potency against purified human factor Xa (fXa) and in a rabbit model of arteriovenous shunt thrombosis for their antithrombotic activities, expressed as K(..
  91. ncbi FXa-induced responses in vascular wall cells are PAR-mediated and inhibited by ZK-807834
    K McLean
    Berlex Biosciences, Richmond, CA 94804, USA
    Thromb Res 103:281-97. 2001
    ..vascular wall cells are exposed to clotting factors, including the procoagulant proteases thrombin and factor Xa (FXa), both known to induce cell signaling...
  92. ncbi Fondaparinux: a Factor Xa inhibitor for antithrombotic therapy
    Alexander G G Turpie
    Hamilton Health Sciences General Hospital, Department of Medicine, 237 Barton Street East, Hamilton, Ontario, L8L 2X2, Canada
    Expert Opin Pharmacother 5:1373-84. 2004
    Fondaparinux (Arixtra) is the first of a new class of antithrombotic compounds - Factor Xa inhibitors. This synthetic pentasaccharide acts by inhibiting Factor Xa selectively...
  93. ncbi Isoxazolines and isoxazoles as factor Xa inhibitors
    J R Pruitt
    The DuPont Pharmaceuticals Company, Wilmington, Delaware 19880 0500, USA
    Bioorg Med Chem Lett 10:685-9. 2000
    ..They were compared to 3,5,5-trisubstituted isoxazolines (1) for Factor Xa selectivity and potency. They were also compared in an arterio-venous (A-V) shunt model of thrombosis.
  94. ncbi Blood coagulation
    S Butenas
    University of Vermont, Department of Biochemistry, Burlington, VT 05405 0068, USA
    Biochemistry (Mosc) 67:3-12. 2002
    ..The majority of data accumulated in in vitro models and discussed in this review are in good agreement with the results of in vivo observations...
  95. ncbi Elevated plasma levels of the factor Xa-TFPI complex in cancer patients
    Nina Iversen
    Haematological Research Laboratory, Department of Medicine, Aker Hospital, University of Oslo, N 0514 Oslo, Norway
    Thromb Res 105:33-6. 2002
    ..We now report that also the median plasma levels of the Factor Xa (FXa)-TFPI complex were significantly higher in patients with solid tumours, compared to patients with ..
  96. ncbi Beyond unfractionated heparin and warfarin: current and future advances
    Jack Hirsh
    Henderson Research Centre, Hamilton Health Sciences Corporatin, Ontario, Canada
    Circulation 116:552-60. 2007
  97. pmc Computationally derived points of fragility of a human cascade are consistent with current therapeutic strategies
    Deyan Luan
    Department of Chemical and Biomolecular Engineering, Cornell University, Ithaca, New York, USA
    PLoS Comput Biol 3:e142. 2007
    ..When taken together, these results support our working hypothesis that computationally derived points of fragility of human relevant cascades could be used as a rational basis for target selection despite model uncertainty...
  98. ncbi Bleeding in patients using new anticoagulants or antiplatelet agents: risk factors and management
    M M Levi
    Department of Vascular Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
    Neth J Med 68:68-76. 2010
    ..The new-generation anticoagulants include specific inhibitors of factor IIa or factor Xa (including pentasaccharides) and antiplatelet agents belonging to the class of thienopyridine derivatives...
  99. pmc Ixolaris binding to factor X reveals a precursor state of factor Xa heparin-binding exosite
    Robson Q Monteiro
    Instituto de Bioquimica Medica, Centro de Ciencias de Saude, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
    Protein Sci 17:146-53. 2008
    ..In contrast to human TFPI, Ixolaris specifically binds to factor Xa (FXa) heparin-binding exosite (HBE). In addition, Ixolaris interacts with zymogen FX...
  100. ncbi Heparin derivatives as inhibitors of BACE-1, the Alzheimer's beta-secretase, with reduced activity against factor Xa and other proteases
    Susannah J Patey
    School of Biological Sciences, University of Liverpool, Liverpool, L69 7ZB, United Kingdom
    J Med Chem 49:6129-32. 2006
    ..at the principal positions of O-sulfation and N-sulfation/acetylation and tested for BACE-1 inhibitory and anti factor Xa activities...

Research Grants66

  1. MOLECULAR BIOLOGY OF HUMAN COAGULATION FACTOR V
    Thomas Ortel; Fiscal Year: 2010
    ..The prothrombinase complex consists of the enzyme factor Xa, the cofactor factor Va and a phospholipid membrane surface...
  2. Dual Direct Inhibitors of Thrombin and Factor Xa
    UMESH RAMANLAL DESAI; Fiscal Year: 2012
    ..3) Mechanistically, the new molecules inhibit thrombin, factor Xa and factor XIa with IC50 values in the range of 10-240 nM...
  3. PROTEINS OF COAGULATION PATHWAYS
    John H Griffin; Fiscal Year: 2013
    ..and on prothrombinase assays, we hypothesize that the anticoagulant soluble lipids bind and directly inhibit factor Xa. Preliminary data show that certain anticoagulant plasma lipids bind and inhibit Gla-domainless-factor Xa, ..
  4. Membrane Receptors Regulating Megakaryocyte Endocytosis of Factor V from Plasma
    BETH BOUCHARD; Fiscal Year: 2012
    ..by the prothrombinase complex, a 1:1, Ca2+-dependent complex of the cofactor factor Va and the serine protease factor Xa bound to activated platelets adhered to sites of vascular injury...
  5. MOLECULAR BASIS OF BLOOD COAGULATION REGULATION
    Steven T Olson; Fiscal Year: 2013
    ..by heparin in showing that activation is mediated principally by the relief of repulsive interactions with factor Xa and factor IXa and secondarily by the relief of structural constraints of the reactive site that promote ..
  6. Structure and Stability Studies of Factor VIII to Overcome the Immune Response
    PAUL CLINTON SPIEGEL; Fiscal Year: 2010
    ..response result in antibodies that block the activation of factor VIII by the serine proteases, thrombin or factor Xa. These "non-classical" antibodies possess a high level of pathogenicity and display positive cooperativity with "..
  7. Lipid Regulation of Thrombin Generation
    Barry R Lentz; Fiscal Year: 2012
    ..molecule of blood coagulation, is produced by prothrombin (II) proteolysis by a platelet-membrane-bound enzyme (factor Xa) and its associated cofactor (factor Va). The membrane accelerates II activation by 105-fold...
  8. TFPI ALPHA AND TFPI BETA
    George J Broze; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Tissue factor pathway inhibitor (TFPI) produces factor Xa (FXa)-dependent feedback inhibition of factor VIIa/tissue factor (FVIIa/TF)-induced coagulation. In humans, TFPI is expressed as two isoforms...
  9. Structure and Function of the Factor VIII - von Willebrand Factor Complex
    JOHN S LOLLAR; Fiscal Year: 2010
    ..the identification of a novel class of C2 domain Abs that inhibit the activation of fVIII by either thrombin or factor Xa. These Abs make a dominant contribution to the inhibitory immune response to fVIII in hemophilia A mice and in ..
  10. PROTEIN Z DEPENDENT PROTEINASE INHIBITOR
    George J Broze; Fiscal Year: 2011
    Protein Z (PZ) is a vitamin K-dependent plasma protein that serves as a cofactor for the inhibition of factor Xa by PZ-dependent Protease Inhibitor (ZPI)...
  11. INTERACTION OF PLATELETS WITH COAGULATION FACTORS IX & X
    Peter Walsh; Fiscal Year: 1992
    Platelets possess specific, high-affinity, saturable receptors for factor XI, factor XIa, factor Xa, thrombin, high molecular weight kininogen, and factor Va and promote the proteolytic activation of factor XII, factor XI, factor X, and ..
  12. Chemical and enzymatic synthesis of multi-domain heparin mimetics
    TIMOTHY OLEARY; Fiscal Year: 2013
    ..Heparin bound to AT inhibits the coagulation cascade enzymes factor Xa and factor IIa (thrombin)...
  13. Studies on Na+ binding to thrombin
    Enrico Di Cera; Fiscal Year: 2010
    ..griseus and tissue-type plasminogen activator, to introduce Na+ activation as found in human thrombin and factor Xa, and molecular mimicry of Na+ activation as found in murine thrombin...
  14. METAL DEPENDENT COMPLEXES IN BLOOD COAGULATION
    Barbara Furie; Fiscal Year: 2002
    ..In addition, studies are proposed to determine sites of interaction between factor Va and factor Xa and between factor Va and prothrombin...
  15. ANTIBODIES WITH PROTHROMBINASE ACTIVITY IN LUPUS
    Perumal Thiagarajan; Fiscal Year: 2003
    ..g., antibody mediated inhibition of prothrombin activation by factor Xa; accelerated prothrombin clearance)...
  16. MOLECULAR INTERACTIONS OF BLOOD COAGULATION FACTOR XA
    Katherine High; Fiscal Year: 1999
    ..Once activated, it participates in formation of the prothrombinase complex, composed of Factor Xa (F.Xa) and the cofactor Factor Va (F.Va) on a membrane surface in the presence of calcium ions...
  17. FACTOR VA INTERACTIONS REGULATING PROTHROMBIN ACTIVATION
    Paul E Bock; Fiscal Year: 2010
    ..and its activation intermediates that order the pathway and control the generation of specific binding sites for factor Xa and ProT...
  18. The Prothrombinase Complex: A Model of an Enzyme-Cofactor Complex
    MARIA CRISTINA BRAVO; Fiscal Year: 2010
    ..The prothrombinase complex, formed between a noncovalent association between the enzyme factor Xa and cofactor Va, serves as the final generator of thrombin...
  19. MOLECULAR INTERACTIONS OF BLOOD COAGULATION FACTOR X
    RICHARD PAINTER; Fiscal Year: 1991
    ..Once activated, factor Xa (enzyme) associates with factor Va (cofactor) in another membrane surface complex responsible for the activation ..
  20. The role of coagulation cascade proteases in pleural fibrosis
    TORRY ALLE TUCKER; Fiscal Year: 2013
    ..Our preliminary data support the concept that procoagulants induce MT. The role of factor Xa and thrombin in MT is now unknown and will be elucidated in this project. Dr...
  21. Protein interactions by analytical ultracentrifugation
    PETER GETTINS; Fiscal Year: 2007
    ..forms, organization of crmA-caspase complexes, and studies on the complex formed between ZPI, protein Z and factor Xa that permits inhibition of factor Xa by ZPI (Olson)...
  22. Structure-function of cytoprotective coagulation proteases and their receptors
    LAURENT OLIVIER MOSNIER; Fiscal Year: 2013
    ..g. thrombin and factor Xa) on cells and initiated novel perspectives on the intricate complex networks of receptor-mediated cross talk in ..
  23. Thrombin Formation Inhibitors
    James Phillips; Fiscal Year: 2004
    ..Prothrombinase is composed of the protein cofactor, factor Va, and the enzyme, factor Xa, associated on a cell surface in the presence of divalent metal ions...
  24. Novel Self-Limiting Prothrombinase Inhibitors
    MICHAEL N BLACKBURN; Fiscal Year: 2012
    ..Our access to such 3D structures of Factor Xa makes this work possible. The specific aims of this work are to: 1...
  25. Targeted Anticoagulant Therapy for Sickle Cell Disease
    RAFAL L PAWLINSKI; Fiscal Year: 2013
    ..In a complementary proof-of-concept clinical trial with the newly available factor Xa (FXa) inhibitor rivaroxaban, we will determine whether the effect of FXa inhibition extends beyond simple ..
  26. AUTOIMMUNE MECHANISMS OF THROMBOSIS
    Robert Roubey; Fiscal Year: 2004
    ..and autoantibodies to tissue factor pathway inhibitor (TFPI), a critical inhibitor of both factor VIIa/TF and factor Xa. Whole blood TF activity in APS patients will be measured to determine if certain autoantibodies are associated ..
  27. The Molecular Pathogenesis of Hookworm Anemia
    Michael Cappello; Fiscal Year: 2005
    ..ceylanicum RNA, and the recombinant protein inhibits the activity of coagulation factor Xa by a novel mechanism...
  28. The Molecular Pathogenesis of Hookworm Anemia
    Michael Cappello; Fiscal Year: 2001
    ..ceylanicum RNA, and the recombinant protein inhibits the activity of coagulation factor Xa by a potentially novel mechanism...
  29. DEFINITION OF FUNCTIONAL SITES ON COAGULATION FACTOR X
    WILLIAM CHURCH; Fiscal Year: 1993
    ....
  30. MEMBRANE BIOPHYSICS AND CONTROL OF THROMBIN GENERATION
    BARRY LENTZ; Fiscal Year: 1999
    ..in regulating prothrombin activation because it apparently serves to assemble the prothrombinase, activate factor Xa, place the appropriate peptide bond of prothrombin near the factor Xa active site, and then channel the ..
  31. Processed Defining Megakaryocyte Endocytosis of Factor V
    PAULA TRACY; Fiscal Year: 2005
    ..consists of 1:1, stoichiometric, calcium-dependent complex of the cofactor factor Va and the serine protease factor Xa bound to activated platelets...
  32. NMR STRUCTURES OF PLATELET FACTOR 4 & B-THROMBOGLOBULIN
    Kevin Mayo; Fiscal Year: 1992
    ..it possesses significant mitogenic activity in certain cell types and inhibits the catalytic effect heparin on Factor Xa neutralization by anti-thrombin IIIa more than does PF4...
  33. PROTHROMBIN ACTIVATION ON BLOOD MONONUCLEAR CELLS
    PAULA TRACY; Fiscal Year: 1990
    ..coagulation enzyme prothrombinase, which consists of a membrane-bound, Ca++-dependent complex of factor Va and factor Xa. The primary objective of this proposal is to provide a quantitative understanding of the molecular and ..
  34. ROLE OF TICK SALIVA IN LYME DISEASE AND VACCINE STRATEGY
    Thomas Mather; Fiscal Year: 2006
    ..scapularis' salivary anti-complement protein (Isac) and a Factor Xa-inhibiting anticoagulant (Ixolaris), and recombinant proteins are in production...
  35. ROLE OF TICK SALIVA IN LYME DISEASE AND VACCINE STRATEGY
    Thomas Mather; Fiscal Year: 2001
    ..scapularis' salivary anti-complement protein (Isac) and a Factor Xa-inhibiting anticoagulant (Ixolaris), and recombinant proteins are in production...
  36. PROCOAGULANT PROPERTIES OF THE SICKLE CELL MEMBRANE
    Jolyon Jesty; Fiscal Year: 1992
    ..major clotting reactions: the activation of factor X by the factor IXa-VIIIa complex, and of prothrombin by the factor Xa-Va complex...
  37. SUBSTRATE RECOGNITION IN BLOOD COAGULATION
    Sriram Krishnaswamy; Fiscal Year: 2003
    ..By comparing the function of factor Xa with prothrombinase, we will determine if modulation of binding interactions can explain the increased Vmax for ..
  38. PROTHROMBINASE COMPLEX--STOPPED-FLOW KINETICS
    Sriram Krishnaswamy; Fiscal Year: 1991
    Prothrombinase is the coagulation complex composed of the serine protease factor Xa, the protein cofactor factor Va, phospholipid or cellular surface and calcium ions...
  39. FACTOR VA INTERACTIONS REGULATING PROTHROMBIN ACTIVATION
    Paul Bock; Fiscal Year: 1991
    ..The interdependent interactions among factor Xa (enzyme), prothrombin (substrate), factor Va (cofactor) and the surfaces of blood platelets are required to ..
  40. HEPARIN AND BLOOD COAGULATION
    ISIDORE DANISHEFSKY; Fiscal Year: 1991
    ..specific focus of our investigations will be on the interaction of antithrombin with thrombin and coagulation- factor Xa, and the actions of heparin on these processes...
  41. Thrombus Formation Initiation and Propagation
    Barbara Furie; Fiscal Year: 2007
    ..through exposure of tissue factor at sites of vascular injury resulting in the generation of small quantities of factor Xa and thrombin...
  42. A Novel Family of Anticoagulants from Ixodes scapularis
    Michel Ledizet; Fiscal Year: 2003
    ..This tick's saliva contains potent anticoagulants, including a Factor Xa inhibitor. Purified salivary proteins with anticoagulant activity were subjected to N-terminal sequencing...
  43. Molecular Recognition in Factor VIIa Induced Coagulation
    S Bajaj; Fiscal Year: 2005
    ..Tissue factor pathway inhibitor (TFPI) contains two functional Kunitz domains (K1 and K2) and it first inhibits factor Xa via its K2 domain...
  44. BLOOD COAGULATION HOMESTASIS: REGULATION OF TFPI
    Alan Schwartz; Fiscal Year: 2003
    ..which produces feedback inhibition of the factor VIIa/tissue factor complex and directly binds and inhibits factor Xa. TFPI is rapidly cleared in vivo via the endocytosis receptor, LRP (low density lipoprotein receptor-related ..
  45. NOVEL ANTITHROMBOTIC AGENT
    David Wolf; Fiscal Year: 1993
    ..The complex consists of factor Xa (a serine protease), factor Va (a co-factor) and Ca2+ assembled on phospholipid surfaces...
  46. THE STRUCTURE AND FUNCTION OF PLATELET GPIIB-IIIA
    Edward Plow; Fiscal Year: 2003
    ..Bound prothrombin is more readily activated to thrombin by Factor Xa, and thrombin is released from the receptor to stimulate platelets and activate alphaIIbbeta3, which then ..
  47. STRUCTURE OF PROTEINS OF THE RIBOSE TRANSPORT SYSTEM
    Mark Hermodson; Fiscal Year: 2000
    ..largely membrane-embedded), and RbsA-C (a chimeric protein containing all of RbsA joined to RbsC by a flexible factor Xa-cleavable bridge)...
  48. NOVEL ANTITHROMBOTIC AGENT
    David Wolf; Fiscal Year: 1990
    ..Thrombin is generated from the zymogen prothrombin by the prothrombinase complex which consists of factor Xa (a serine protease), factor Va (a co-factor) and Ca2+ assembled on a phospholipid surface...
  49. Antithrombin targeting to HSPG & heparin coated surfaces
    Susan Bock; Fiscal Year: 2006
    Activation of thrombin and factor Xa (fXa) occurs on vascular and biomaterial surfaces and initiates coagulation, platelet, signaling and cell proliferation reactions, which may then promote pathological thrombosis, occlusion and ..
  50. THROMBOGENIC PHOSPHOLIPID SURFACES
    FREDERICK DOMBROSE; Fiscal Year: 1980
    ..of: a) its ability to bind prothrombin; and b) enhance the rate of conversion of prothrombin to thrombin by Factor Xa in the presence of an optimal concentration of calcium ions, in vitro (functional definition of thrombogenicity)...
  51. MOLECULAR INTERACTIONS IN INFLAMMATION AND COAGULATION
    Charles Esmon; Fiscal Year: 1999
    ..the molecular mechanisms responsible for the restricted substrate specificity exhibited by thrombin, APC, and factor Xa, and the molecular mechanisms by which the cofactors modulate the function of these enzymes...
  52. MOLECULAR BASIS OF COAGULATION PROTEASE SPECIFICITY
    Alireza R Rezaie; Fiscal Year: 2010
    ....
  53. MOLECULAR REGULATION OF ARTERIAL THROMBOSIS
    Robert Simari; Fiscal Year: 2009
    ..uniquely modifies the coagulation cascade in vivo by binding to TF-factor Vila (via the K1 domain) and factor Xa (via the K2 domain) forming an inhibitory complex which dampens further coagulation...
  54. Novel Anticoagulant Mechanisms
    MARY HEEB; Fiscal Year: 2006
    ..focus on a novel coagulation regulator, protein Z-dependent protease inhibitor (ZPI) that rapidly inactivates Factor Xa (FXa) in the presence of protein Z, Ca 2+ and phospholipids (PL)...
  55. FORMS OF PROSTATE SPECIFIC ANTIGEN AND HK2 IN CANCER
    MARY HEEB; Fiscal Year: 2003
    ..Techniques will include protein purification, antibody and ELISA development, immunoblotting, enzyme activity assays, and peptide synthesis. ..
  56. Nanoparticle targeting of cathepsin-L inhibitor and doxorubicin in breast cancer
    Shaker Mousa; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  57. SERPIN-PROTEASE REACTION, HYDRATION AND GEOMETRY CHANGES
    Maria McGee; Fiscal Year: 2002
    ..This information will serve to develop therapies to prevent and control thromboembolic complications of cardiovascular disease. ..
  58. Functional Domains of Coagulation Factor V
    Michael Kalafatis; Fiscal Year: 2007
    Prothrombinase is composed of the protein cofactor, factor Va, and the enzyme, factor Xa, associated on a cell surface in the presence of divalent metal ions...
  59. OU Developmental Center for Injury Prevention Research
    Gary Raskob; Fiscal Year: 2005
    ..abstract_text> ..
  60. OU Human Research Protection Program, Year 2
    Gary Raskob; Fiscal Year: 2003
    ..The University of Oklahoma is committed to maintaining these initiatives after the term of this award. ..
  61. Structural Mechanisms for the Inhibition of Thrombosis
    JAMES HUNTINGTON; Fiscal Year: 2009
    ..of the blood coagulation cascade: 1) prevention of thrombin formation through inhibition of upstream coagulation factor Xa;2) direct inhibition of thrombin by serpins antithrombin (AT) and heparin cofactor II (HCII);and, 3) attenuation ..
  62. TARGETING SIGNALING OF THE TISSUE FACTOR PATHWAY
    Wolfram Ruf; Fiscal Year: 2007
    ..abstract_text> ..
  63. MOLECULAR BASIS OF BLOOD COAGULATION REGULATION
    Steven Olson; Fiscal Year: 2009
    ..We propose to map these exosite regions on antithrombin and on factor Xa and factor IXa and determine the mechanism by which the exosites mediate heparin rate enhancement of ..
  64. Chronic Thromboembolic Pulmonary Hypertension
    TIMOTHY MORRIS; Fiscal Year: 2006
    ..The fragments will be subjected to liquid chromatography-mass spectroscopy with data-dependent MS-2 data acquisition, followed by computer-assisted sequence analysis. ..
  65. PAR SIGNALING AND PROTECTIVE PATHWAYS IN INFLAMMATION AND SEPSIS
    Wolfram Ruf; Fiscal Year: 2010
    ..3. ..