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. doi 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
  2. doi 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
  3. 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
  4. doi 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
  5. doi 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
  6. doi 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
  7. doi 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
  8. doi 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
  9. 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
  10. 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

Research Grants

  1. Dual Direct Inhibitors of Thrombin and Factor Xa
    Umesh Desai; Fiscal Year: 2009
  2. Dual Direct Inhibitors of Thrombin and Factor Xa
    UMESH RAMANLAL DESAI; Fiscal Year: 2010
  3. MOLECULAR BIOLOGY OF HUMAN COAGULATION FACTOR V
    WILLIAM KANE; Fiscal Year: 2009
  4. MOLECULAR BIOLOGY OF HUMAN COAGULATION FACTOR V
    Thomas Ortel; Fiscal Year: 2010
  5. Lipid Regulation of Thrombin Generation
    Barry R Lentz; Fiscal Year: 2010
  6. METAL DEPENDENT COMPLEXES IN BLOOD COAGULATION
    Barbara Furie; Fiscal Year: 2002
  7. Lipid Regulation of Thrombin Generation
    Barry R Lentz; Fiscal Year: 2010
  8. ANTIBODIES WITH PROTHROMBINASE ACTIVITY IN LUPUS
    Perumal Thiagarajan; Fiscal Year: 2003
  9. GLUCOSE TRANSPORTER STRUCTURE AND FUNCTION
    Anthony Carruthers; Fiscal Year: 2009
  10. GLUCOSE TRANSPORTER STRUCTURE AND FUNCTION
    Anthony Carruthers; Fiscal Year: 2010

Detail Information

Publications300 found, 100 shown here

  1. doi 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...
  2. doi 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...
  3. 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...
  4. doi 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.
  5. doi 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.
  6. doi 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...
  7. doi 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...
  8. doi 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.
  9. 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...
  10. 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 ..
  11. 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...
  12. doi 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...
  13. 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...
  14. doi 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...
  15. doi 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 ..
  16. 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...
  17. doi 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-..
  18. 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...
  19. doi 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...
  20. 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 ..
  21. 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...
  22. doi 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...
  23. 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...
  24. 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...
  25. doi 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 ..
  26. 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...
  27. 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...
  28. doi 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...
  29. 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...
  30. 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).
  31. doi 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...
  32. 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...
  33. 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...
  34. 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...
  35. 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...
  36. doi 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...
  37. doi 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...
  38. doi 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.
  39. 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...
  40. 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...
  41. 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...
  42. doi 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 ..
  43. 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 ..
  44. 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...
  45. 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-..
  46. 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...
  47. 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...
  48. 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...
  49. doi 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...
  50. 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(..
  51. doi 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...
  52. 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.
  53. 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...
  54. 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 ..
  55. doi 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...
  56. 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...
  57. doi 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...
  58. 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...
  59. doi 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.
  60. 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
  61. 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...
  62. 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...
  63. doi Coagulation signalling following tissue injury: focus on the role of factor Xa
    Malvina A Krupiczojc
    Centre for Respiratory Research, University College London, London, UK
    Int J Biochem Cell Biol 40:1228-37. 2008
    ..However, recent evidence suggests that coagulation proteinases upstream of thrombin, including factor Xa (FXa), may also signal via PARs and thus induce cellular effects independent of thrombin generation...
  64. 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...
  65. ncbi Anti-Xa activity relates to survival and efficacy in unselected acute coronary syndrome patients treated with enoxaparin
    G Montalescot
    Institut de Cardiologie, Pitie Salpetriere Hospital, Paris, France
    Circulation 110:392-8. 2004
    ....
  66. doi Discovery of a factor Xa inhibitor (3R,4R)-1-(2,2-difluoro-ethyl)-pyrrolidine-3,4-dicarboxylic acid 3-[(5-chloro-pyridin-2-yl)-amide] 4-[[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenyl]-amide] as a clinical candidate
    Lilli Anselm
    F Hoffmann La Roche Ltd, Pharma Research, Basel, Switzerland
    Bioorg Med Chem Lett 20:5313-9. 2010
    A series of (3R,4R)-pyrrolidine-3,4-dicarboxylic acid amides was investigated with respect to their factor Xa inhibitory activity, selectivity, pharmacokinetic properties, and ex vivo antithrombotic activity...
  67. doi Discovery of betrixaban (PRT054021), N-(5-chloropyridin-2-yl)-2-(4-(N,N-dimethylcarbamimidoyl)benzamido)-5-methoxybenzamide, a highly potent, selective, and orally efficacious factor Xa inhibitor
    Penglie Zhang
    Millennium Pharmaceuticals, Inc, South San Francisco, CA 94080, USA
    Bioorg Med Chem Lett 19:2179-85. 2009
    Systematic SAR studies of in vitro factor Xa inhibitory activity around compound 1 were performed by modifying each of the three phenyl rings...
  68. doi Oral direct factor Xa inhibition with edoxaban for thromboprophylaxis after elective total hip replacement. A randomised double-blind dose-response study
    Gary Raskob
    College of Public Health, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA
    Thromb Haemost 104:642-9. 2010
    Edoxaban is a new oral direct factor Xa inhibitor...
  69. pmc Factor Xa stimulates proinflammatory and profibrotic responses in fibroblasts via protease-activated receptor-2 activation
    Keren Borensztajn
    Center for Experimental and Molecular Medicine, Academic Medical Center, Meibergdreef 9, NL 1105 AZ, Amsterdam, The Netherlands
    Am J Pathol 172:309-20. 2008
    ..Taken together, these results support the notion that, beyond its role in coagulation, FXa-dependent PAR-2 cleavage might play a role in the progression of tissue fibrosis and remodeling...
  70. 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...
  71. ncbi Effects of factor Xa and protein S on the individual activated protein C-mediated cleavages of coagulation factor Va
    Eva A Norstrøm
    Department of Laboratory Medicine, Clinical Chemistry, Lund University, The Wallenberg Laboratory, University Hospital, Malmo, SE 205 02 Malmo, Sweden
    J Biol Chem 281:31486-94. 2006
    ..The cleavage at Arg-506 is kinetically favored but protected by factor Xa (FXa)...
  72. doi 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...
  73. ncbi Pharmacophore identification, in silico screening, and virtual library design for inhibitors of the human factor Xa
    Eva M Krovat
    Department of Pharmaceutical Chemistry, Institute of Pharmacy, University of Innsbruck, Innrain 52a, 6020 Innsbruck, Austria
    J Chem Inf Model 45:146-59. 2005
    b>Factor Xa inhibitors are innovative anticoagulant agents that provide a better safety/efficacy profile compared to other anticoagulative drugs...
  74. pmc Coagulation factor Xa modulates airway remodeling in a murine model of asthma
    Kazuhiko Shinagawa
    WM Keck Center for Transgene Research, University of Notre Dame, Notre Dame, IN 46556, USA
    Am J Respir Crit Care Med 175:136-43. 2007
    ..Previous studies have demonstrated that dysregulated coagulation and fibrinolysis contribute to the pathogenesis of asthma...
  75. doi Factors influencing enoxaparin anti-Xa activity in surgical critically ill patients
    Philippe D Vincent
    Department of Pharmacy Services, Louis H Lafontaine Hospital, Montreal, Canada H1N 3M5
    J Crit Care 26:347-51. 2011
    ..The objectives of the present study were to describe the incidence of low anti-Xa levels defined as below 0.1 IU/mL in a general surgical intensive care unit population and to evaluate factors independently influencing anti-Xa activity...
  76. 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...
  77. doi Effects of the oral, direct factor Xa inhibitor rivaroxaban on commonly used coagulation assays
    A Hillarp
    University and Regional Laboratories Region Scania, Clinical Chemistry, Malmo, Sweden
    J Thromb Haemost 9:133-9. 2011
    Rivaroxaban is an oral direct factor Xa inhibitor developed for prophylaxis and treatment of thromboembolic disorders...
  78. 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...
  79. doi A zymogen-like factor Xa variant corrects the coagulation defect in hemophilia
    Lacramioara Ivanciu
    Department of Pediatrics, Division of Hematology, The Children s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
    Nat Biotechnol 29:1028-33. 2011
    ..We improve hemostasis in vivo using a conformationally pliant variant of coagulation factor Xa (FXa(I16L)) rendered partially inactive by a defect in the transition from zymogen to active protease...
  80. doi Comparison of antithrombotic and haemorrhagic effects of edoxaban, an oral direct factor Xa inhibitor, with warfarin and enoxaparin in rats
    Yoshiyuki Morishima
    Biological Research Laboratories, R and D Division, Daiichi Sankyo Co, Ltd, 1 2 58 Hiromachi, Shinagawa ku, Tokyo 140 8710, Japan
    Thromb Res 130:514-9. 2012
    b>Factor Xa (FXa) is a key serine protease in the coagulation cascade and a promising target for a new antithrombotic agent. Edoxaban is an oral, selective and direct FXa inhibitor...
  81. doi Recent progress in anticoagulant therapy: oral direct inhibitors of thrombin and factor Xa
    K A Bauer
    VA Boston Healthcare System and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
    J Thromb Haemost 9:12-9. 2011
    ..New oral anticoagulants that selectively inhibit either thrombin (dabigatran etexilate) or factor Xa (rivaroxaban, apixaban) have now gained approval in many countries for some clinical indications...
  82. 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...
  83. ncbi Mapping of the catalytic groove preferences of factor Xa reveals an inadequate selectivity for its macromolecule substrates
    Elsa P Bianchini
    INSERM U428, Faculte de Pharmacie, Universite Paris V, Paris, France
    J Biol Chem 277:20527-34. 2002
    b>Factor Xa (FXa) hydrolyzes two peptide bonds in prothrombin having (Glu/Asp)-Gly-Arg-(Thr/Ile) for P(3)-P(2)-P(1)-P(1)' residues, but the exact preferences of its catalytic groove remain largely unknown...
  84. ncbi Elimination of P1 arginine 393 interaction with underlying glutamic acid 255 partially activates antithrombin III for thrombin inhibition but not factor Xa inhibition
    Mohamad Aman Jairajpuri
    Department of Medicine, University of Utah, Salt Lake City, Utah 84132, USA
    J Biol Chem 277:24460-5. 2002
    ..In the absence of cofactor, E255A exhibited a 5-fold activation of thrombin inhibition but no activation of factor Xa inhibition...
  85. ncbi Rivaroxaban, an oral direct factor Xa inhibitor
    Jonathan P Piccini
    Duke University Medical Center, Duke Clinical Research Institute, 2400 Pratt Street, 7581, Durham, NC 27705, USA
    Expert Opin Investig Drugs 17:925-37. 2008
    Rivaroxaban is a small molecule, direct Factor Xa inhibitor and may be a potentially attractive alternative to vitamin K antagonists. Rivaroxaban is being investigated for the prevention and treatment of venous and arterial thrombosis...
  86. ncbi Heparin-binding exosite of factor Xa
    A R Rezaie
    Edward A Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, MO 63104, USA
    Trends Cardiovasc Med 10:333-8. 2000
    ..Lys(169), Lys(236), and Arg(240) (chymotrypsin numbering) constitute an exosite in the catalytic domain of factor Xa that can effectively bind heparin only if the acidic N-terminal Gla domain of the proteinase was neutralized by ..
  87. doi The mechanism of action of rivaroxaban--an oral, direct Factor Xa inhibitor--compared with other anticoagulants
    Meyer Michel Samama
    Hotel Dieu University Hospital, Paris, France
    Thromb Res 127:497-504. 2011
    ..their anticoagulant effect via direct inhibition of a single Factor within the coagulation cascade (such as Factor Xa or thrombin)...
  88. pmc A computational modeling and molecular dynamics study of the Michaelis complex of human protein Z-dependent protease inhibitor (ZPI) and factor Xa (FXa)
    Vasudevan Chandrasekaran
    Department of Chemistry, University of North Carolina, Chapel Hill, NC, USA
    J Mol Model 15:897-911. 2009
    ..ZPI) and antithrombin III (AT3) are members of the serpin superfamily of protease inhibitors that inhibit factor Xa (FXa) and other proteases in the coagulation pathway...
  89. pmc Kinetic characterization of the protein Z-dependent protease inhibitor reaction with blood coagulation factor Xa
    Xin Huang
    Center for Molecular Biology of Oral Diseases, University of Illinois at Chicago, Chicago, Illinois 60612, USA
    J Biol Chem 283:29770-83. 2008
    ..Here we show that ZPI and its cofactor, protein Z (PZ), inhibit procoagulant membrane-bound factor Xa by the branched pathway acyl-intermediate trapping mechanism used by other serpins, but with significant ..
  90. doi Biarylmethoxy isonipecotanilides as potent and selective inhibitors of blood coagulation factor Xa
    Gianfranco Lopopolo
    Dipartimento Farmaco Chimico, University of Bari, Via E Orabona 4, I 70125 Bari, Italy
    Eur J Pharm Sci 42:180-91. 2011
    ..piperidine-4-carboxamides were synthesized and assayed in vitro as inhibitors of the blood coagulation enzymes factor Xa (fXa) and thrombin...
  91. ncbi Crystal structures of two potent nonamidine inhibitors bound to factor Xa
    Marc Adler
    Berlex Biosciences, 2600 Hilltop Drive, P O Box 4099, Richmond, CA 94804 0099, USA
    Biochemistry 41:15514-23. 2002
    There has been intense interest in the development of factor Xa inhibitors for the treatment of thrombotic diseases. Our laboratory has developed a series of novel non-amidine inhibitors of factor Xa...
  92. ncbi Design, synthesis, and biological activity of non-basic compounds as factor Xa inhibitors: SAR study of S1 and aryl binding sites
    Satoshi Komoriya
    Tokyo R and D Center, Daiichi Pharmaceutical Co Ltd, 16 13 Kita Kasai 1 Chome, Edogawa ku, Tokyo 134 8630, Japan
    Bioorg Med Chem 13:3927-54. 2005
    ..The optimized compounds 73b and 75b showed sub to one digit micromolar anticoagulant activity (PTCT2). Particularly, anti-fXa activity was detected in plasma of rats orally administered with 1mg/kg of compound 75b...
  93. ncbi Assessment of three chromogenic and one clotting assays for the measurement of synthetic pentasaccharide fondaparinux (Arixtra) anti-Xa activity
    F Depasse
    J Thromb Haemost 2:346-8. 2004
  94. ncbi 1-[3-Aminobenzisoxazol-5'-yl]-3-trifluoromethyl-6-[2'-(3-(R)-hydroxy-N-pyrrolidinyl)methyl-[1,1']-biphen-4-yl]-1,4,5,6-tetrahydropyrazolo-[3,4-c]-pyridin-7-one (BMS-740808) a highly potent, selective, efficacious, and orally bioavailable inhibitor of bloo
    Donald J P Pinto
    Discovery Chemistry Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543, USA
    Bioorg Med Chem Lett 16:4141-7. 2006
    Attempts to further optimize the pyrazole factor Xa inhibitors centered on masking the aryl aniline P4 moiety...
  95. ncbi Synthetic selective inhibitors of coagulation factor Xa strongly inhibit thrombin generation without affecting initial thrombin forming time necessary for platelet activation in hemostasis
    M Ieko
    Departments of Internal Medicine, Health Sciences University of Hokkaido, Ishikari Tobetsu, Hokkaido, Japan
    J Thromb Haemost 2:612-8. 2004
    ....
  96. ncbi SAR and X-ray structures of enantiopure 1,2-cis-(1R,2S)-cyclopentyldiamine and cyclohexyldiamine derivatives as inhibitors of coagulation Factor Xa
    Jennifer X Qiao
    Bristol Myers Squibb Company, Research and Development, PO Box 5400, Princeton, NJ 08543 5400, USA
    Bioorg Med Chem Lett 17:4419-27. 2007
    In the search of Factor Xa (FXa) inhibitors structurally different from the pyrazole-based series, we identified a viable series of enantiopure cis-(1R,2S)-cycloalkyldiamine derivatives as potent and selective inhibitors of FXa...
  97. ncbi Thiophene-anthranilamides as highly potent and orally available factor Xa inhibitors
    Bin Ye
    Berlex Biosciences, Post Office Box 4099, Richmond, California 94804 0099, USA
    J Med Chem 50:2967-80. 2007
    There remains a high unmet medical need for a safe oral therapy for thrombotic disorders. The serine protease factor Xa (fXa), with its central role in the coagulation cascade, is among the more promising targets for anticoagulant ..
  98. ncbi Discovery of 1-(3'-aminobenzisoxazol-5'-yl)-3-trifluoromethyl-N-[2-fluoro-4- [(2'-dimethylaminomethyl)imidazol-1-yl]phenyl]-1H-pyrazole-5-carboxyamide hydrochloride (razaxaban), a highly potent, selective, and orally bioavailable factor Xa inhibitor
    Mimi L Quan
    Discovery Chemistry, Pharmaceutical Research Institute, Bristol Myers Squibb Co, P O Box 5400, Princeton, New Jersey 08543 5400, USA
    J Med Chem 48:1729-44. 2005
    Modification of a series of pyrazole factor Xa inhibitors to incorporate an aminobenzisoxazole as the P(1) ligand resulted in compounds with improved selectivity for factor Xa relative to trypsin and plasma kallikrein...
  99. ncbi Roles of coagulation pathway and factor Xa in rat mesangioproliferative glomerulonephritis
    Keiko Nomura
    Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
    Lab Invest 87:150-60. 2007
    Tissue factor initiates the extrinsic coagulation pathway by activating coagulation factor X to factor Xa, and factor V is a cofactor for the prothrombin activation by factor Xa...
  100. ncbi First experience with direct, selective factor Xa inhibition in patients with non-ST-elevation acute coronary syndromes: results of the XaNADU-ACS Trial
    J H Alexander
    Duke University Center and Duke Clinical Research Institute, Durham, NC 27715, USA
    J Thromb Haemost 3:439-47. 2005
    ..Anticoagulants with predictable kinetics and anticoagulant effects, better efficacy, and greater safety are needed...

Research Grants89

  1. Dual Direct Inhibitors of Thrombin and Factor Xa
    Umesh Desai; Fiscal Year: 2009
    ..3) Mechanistically, the new molecules inhibit thrombin, factor Xa and factor XIa with IC50 values in the range of 10-240 nM...
  2. Dual Direct Inhibitors of Thrombin and Factor Xa
    UMESH RAMANLAL DESAI; Fiscal Year: 2010
    ..3) Mechanistically, the new molecules inhibit thrombin, factor Xa and factor XIa with IC50 values in the range of 10-240 nM...
  3. MOLECULAR BIOLOGY OF HUMAN COAGULATION FACTOR V
    WILLIAM KANE; Fiscal Year: 2009
    ..The prothrombinase complex consists of the enzyme factor Xa, the cofactor factor Va and a phospholipid membrane surface...
  4. 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...
  5. Lipid Regulation of Thrombin Generation
    Barry R Lentz; Fiscal Year: 2010
    ..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...
  6. 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...
  7. Lipid Regulation of Thrombin Generation
    Barry R Lentz; Fiscal Year: 2010
    ..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. ANTIBODIES WITH PROTHROMBINASE ACTIVITY IN LUPUS
    Perumal Thiagarajan; Fiscal Year: 2003
    ..g., antibody mediated inhibition of prothrombin activation by factor Xa; accelerated prothrombin clearance)...
  9. GLUCOSE TRANSPORTER STRUCTURE AND FUNCTION
    Anthony Carruthers; Fiscal Year: 2009
    ..Reciprocal gain of function studies with GLUT5/GLUT1 chimerae will verify the results. A novel, scanning factor Xa proteolysis technique will also define GLUT exo- and endofacial ligand binding sites...
  10. GLUCOSE TRANSPORTER STRUCTURE AND FUNCTION
    Anthony Carruthers; Fiscal Year: 2010
    ..Reciprocal gain of function studies with GLUT5/GLUT1 chimerae will verify the results. A novel, scanning factor Xa proteolysis technique will also define GLUT exo- and endofacial ligand binding sites...
  11. Tissue Factor Pathway Inhibitor Binding Proteins on Endo
    ALAN MAST; Fiscal Year: 2005
    Tissue factor pathway inhibitor (TFPI) rapidly inhibits both factor Xa and the factor VIIa/tissue factor catalytic complex. Thus, it is thought to be the most important inhibitor of the initiation of blood coagulation...
  12. FACTOR VA INTERACTIONS REGULATING PROTHROMBIN ACTIVATION
    Paul Bock; Fiscal Year: 2007
    ..and its activation intermediates that order the pathway and control the generation of specific binding sites for factor Xa and ProT...
  13. 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...
  14. MOLECULAR BIOLOGY OF HUMAN COAGULATION FACTOR V
    WILLIAM KANE; Fiscal Year: 2004
    ..The prothrombinase complex consists of the enzyme factor Xa, the cofactor factor Va and a phospholipid membrane surface...
  15. Structural Mechanisms for the Inhibition of Thrombosis
    JAMES HUNTINGTON; Fiscal Year: 2007
    ..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) ..
  16. 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) ..
  17. MOLECULAR BIOLOGY OF HUMAN COAGULATION FACTOR V
    WILLIAM KANE; Fiscal Year: 2007
    ..The prothrombinase complex consists of the enzyme factor Xa, the cofactor factor Va and a phospholipid membrane surface...
  18. MOLECULAR BIOLOGY OF HUMAN COAGULATION FACTOR V
    WILLIAM KANE; Fiscal Year: 1993
    ..This complex consists of factor Va, factor Xa, calcium, and a phospholipid surface. The generation of thrombin is a critical reaction during hemostasis...
  19. Factor VIIIa interactions in the intrinsic factor Xase
    Philip J Fay; Fiscal Year: 2010
    ..upon our recent studies showing exosite-dependence for cofactor inactivation by activated protein C (APC) and factor Xa, as well as an important contribution of sequences flanking the P1 Arg residues in APC-catalyzed inactivation of ..
  20. 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)...
  21. PROTEINS OF COAGULATION PATHWAYS
    John H Griffin; Fiscal Year: 2010
    ..we hypothesize that anticoagulant acyl carnitines, including palmitoyl carnitine, directly inhibit coagulation factor Xa by binding to Xa...
  22. Factor Vllla interactions in the intrinsic factor Xase
    Philip Fay; Fiscal Year: 2007
    ..Aim II will examine regulation of factor VIIIa by the inactivating proteinases activated protein C (APC) and factor Xa, with emphasis on examining interactions of exosites using unique proteinase forms...
  23. BIOCHEMISTRY OF NORMAL & ABNORMAL VARIANTS OF FACTOR IX
    S Bajaj; Fiscal Year: 2001
    ..and the second domains of tissue factor pathway inhibitor (TFPI) and in the protease domains of factor VIIa and factor Xa in order to understand the structural basis for the first domain of TFPI to bind to factor VIIa and for the ..
  24. 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...
  25. 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...
  26. NMDA RECEPTOR FUNCTION BY SERINE PROTEASE RECEPTORS
    Stephen Traynelis; Fiscal Year: 2003
    ..many components of serine protease-signaling systems, including precursors to the proteases, thrombin, plasmin, Factor Xa, tissue plasminogen activator (tPaA),urokinase, as well as the brain specific proteases and serpin protease ..
  27. PROTEINS OF COAGULATION PATHWAYS
    John Griffin; Fiscal Year: 1999
    ..with APC; ii) specific residues on the surface of protein S are essential for binding of protein S to factor Va, factor Xa or to C4BP; and iii) similarly, residues on the surface of factor Va are essential for its binding to protein S, ..
  28. 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 ..