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| factor xaSummarySummary: 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
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Publications
Clinical laboratory measurement of direct factor Xa inhibitors: anti-Xa assay is preferable to prothrombin time assayYu Chen Barrett
Bristol Myers Squibb, Princeton, New Jersey, USA
Thromb Haemost 104:1263-71. 2010Apixaban and other factor Xa (FXa) inhibitors are in late-stage clinical development for prevention and treatment of thromboembolic diseases...
In vitro and in vivo studies of the novel antithrombotic agent BAY 59-7939--an oral, direct Factor Xa inhibitorE Perzborn
Cardiovascular Research, Bayer HealthCare AG, Wuppertal, Germany
J Thromb Haemost 3:514-21. 2005BAY 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...
Role of the active-site solvent in the thermodynamics of factor Xa ligand bindingRobert 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 ..
Safety, pharmacodynamics, and pharmacokinetics of single doses of BAY 59-7939, an oral, direct factor Xa inhibitorDagmar 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...
Oral, direct Factor Xa inhibition with BAY 59-7939 for the prevention of venous thromboembolism after total hip replacementB 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...
Specificity of coagulation factor signalingW 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...
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 InfarChristian 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.
Anticoagulation by factor Xa inhibitorsT 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...
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-cC 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-..
New oral anticoagulants in developmentJeffrey 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...
Apixaban versus enoxaparin for thromboprophylaxis after hip replacementMichael 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...
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 inhibitorSusanne 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 ..
The significance of circulating factor IXa in bloodSaulius 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 ..
Anticoagulant activity of a sulfated galactan: serpin-independent effect and specific interaction with factor XaBianca 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...
Clinical pharmacology of direct and indirect factor Xa inhibitorsHans 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 ..
Antithrombin-S195A factor Xa-heparin structure reveals the allosteric mechanism of antithrombin activationDaniel 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...
Perspectives on factor Xa inhibitionR 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...
Structure- and property-based design of factor Xa inhibitors: pyrrolidin-2-ones with acyclic alanyl amides as P4 motifsRobert 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...
Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomised, open-label, non-inferiority trialM G Bousser
Lancet 371:315-21. 2008..49). INTERPRETATION: In patients with atrial fibrillation at risk for thromboembolism, long-term treatment with idraparinux was no worse than vitamin K antagonists in terms of efficacy, but caused significantly more bleeding...
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 candidateLilli Anselm
F Hoffmann La Roche Ltd, Pharma Research, Basel, Switzerland
Bioorg Med Chem Lett 20:5313-9. 2010A 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...
A dose-ranging study evaluating the oral factor Xa inhibitor edoxaban for the prevention of venous thromboembolism in patients undergoing total knee arthroplastyT 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...
Inhibition of restenosis by tissue factor pathway inhibitor: in vivo and in vitro evidence for suppressed monocyte chemoattraction and reduced gelatinolytic activityChristoph 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...
Fondaparinux: a Factor Xa inhibitor for antithrombotic therapyAlexander 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. 2004Fondaparinux (Arixtra) is the first of a new class of antithrombotic compounds - Factor Xa inhibitors. This synthetic pentasaccharide acts by inhibiting Factor Xa selectively...
Synergistic induction of tissue factor by coagulation factor Xa and TNF: evidence for involvement of negative regulatory signaling cascadesAyala 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-..
FXa-induced responses in vascular wall cells are PAR-mediated and inhibited by ZK-807834K 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...
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 faDonald 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...
Isoxazolines and isoxazoles as factor Xa inhibitorsJ 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.
Rivaroxaban: a new oral factor Xa inhibitorElisabeth 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. 2010Rivaroxaban 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...
Assessment of laboratory assays to measure rivaroxaban--an oral, direct factor Xa inhibitorMeyer Michel Samama
Hotel Dieu University Hospital, Paris, France 2Biomnis Laboratory, Ivry sur Seine, France
Thromb Haemost 103:815-25. 2010Although 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...
Nonpeptide factor Xa inhibitors: I. Studies with SF303 and SK549, a new class of potent antithromboticsP C Wong
Cardiovascular Diseases Research, DuPont Pharmaceuticals Company, Wilmington, DE 19880 0400, USA
J Pharmacol Exp Ther 292:351-7. 2000A 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(..
Ixolaris binding to factor X reveals a precursor state of factor Xa heparin-binding exositeRobson 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...
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) trialJohn H Alexander
Duke Clinical Research Institute, Duke University Medical Center, DUMC Box 3850, Durham, NC 27715, USA
Circulation 119:2877-85. 2009After 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.
Oral direct factor Xa inhibition with edoxaban for thromboprophylaxis after elective total hip replacement. A randomised double-blind dose-response studyGary Raskob
College of Public Health, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA
Thromb Haemost 104:642-9. 2010Edoxaban is a new oral direct factor Xa inhibitor...
Bleeding in patients using new anticoagulants or antiplatelet agents: risk factors and managementM 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...
Factor Xa stimulates proinflammatory and profibrotic responses in fibroblasts via protease-activated receptor-2 activationKeren 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...
Preclinical discovery of apixaban, a direct and orally bioavailable factor Xa inhibitorPancras 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...
Recent progress in anticoagulant therapy: oral direct inhibitors of thrombin and factor XaK 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...
Rivaroxaban, an oral direct factor Xa inhibitorJonathan 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. 2008Rivaroxaban 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...
Kinetic characterization of the protein Z-dependent protease inhibitor reaction with blood coagulation factor XaXin 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 ..
The mechanism of action of rivaroxaban--an oral, direct Factor Xa inhibitor--compared with other anticoagulantsMeyer 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)...
Elimination of P1 arginine 393 interaction with underlying glutamic acid 255 partially activates antithrombin III for thrombin inhibition but not factor Xa inhibitionMohamad 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...
Interlaboratory agreement in the monitoring of unfractionated heparin using the anti-factor Xa-correlated activated partial thromboplastin timeA 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...
Mapping of the catalytic groove preferences of factor Xa reveals an inadequate selectivity for its macromolecule substratesElsa P Bianchini
INSERM U428, , , Paris, France
J Biol Chem 277:20527-34. 2002b>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...
The discovery and development of rivaroxaban, an oral, direct factor Xa inhibitorElisabeth Perzborn
Global Therapeutic Research, Pharma R and D, Bayer HealthCare, Wuppertal, Germany
Nat Rev Drug Discov 10:61-75. 2011The activated serine protease factor Xa is a promising target for new anticoagulants...
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...
Heparin-binding exosite of factor XaA 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 ..
Biarylmethoxy isonipecotanilides as potent and selective inhibitors of blood coagulation factor XaGianfranco 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...
Factor Xa is highly protected from antithrombin-fondaparinux and antithrombin-enoxaparin when incorporated into the prothrombinase complexN Brufatto
Departments of Biochemistry and Medicine, Queen's University, Kingston, Ontario K7L 3N6, Canada
J Thromb Haemost 1:1258-63. 2003..Similar results were reported for unfractionated heparin previously [1]. Therefore, in the presence of unfractionated heparin, fondaparinux, or enoxaparin, prothrombinase is profoundly protected from antithrombin...
Crystal structures of two potent nonamidine inhibitors bound to factor XaMarc Adler
Berlex Biosciences, 2600 Hilltop Drive, P.O. Box 4099, Richmond, CA 94804-0099, USA
Biochemistry 41:15514-23. 2002There 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...
Thiophene-anthranilamides as highly potent and orally available factor Xa inhibitorsBin Ye
Berlex Biosciences, Post Office Box 4099, Richmond, California 94804 0099, USA
J Med Chem 50:2967-80. 2007There 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 ..
Antithrombotic effects of DX-9065a, a direct factor Xa inhibitor: a comparative study in humans versus low molecular weight heparinDaichi Shimbo
Cardiovascular Biology Research Laboratory, Mount Sinai School of Medicine, New York, NY 10029, USA
Thromb Haemost 88:733-8. 2002..The clinical effectiveness of the direct FXa inhibitors should be further investigated...
SAR and X-ray structures of enantiopure 1,2-cis-(1R,2S)-cyclopentyldiamine and cyclohexyldiamine derivatives as inhibitors of coagulation Factor XaJennifer X Qiao
Bristol Myers Squibb Company, Research and Development, PO Box 5400, Princeton, NJ 08543 5400, USA
Bioorg Med Chem Lett 17:4419-27. 2007In 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...
Effects of DX-9065a, an inhibitor of factor Xa, on ellagic acid-induced plantar skin thrombosis assessed in tetrodotoxin- and N(omega)-nitro-L-arginine-treated ratsDaisuke Chino
Department of Pharmacology, Faculty of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan
J Pharmacol Sci 91:319-29. 2003..acid hydrochloride pentahydrate), a dibasic propanoic acid and an inhibitor of factor Xa, were compared with those of argatroban, a low molecular weight thrombin inhibitor, on the ellagic acid-induced ..
DX-9065a, a direct inhibitor of factor XaBrigitte Kaiser
Friedrich Schiller University Jena, Medical Faculty, Center for Vascular Biology and Medicine, Nordhäuser Strasse 78, D 99089 Erfurt, Germany
Cardiovasc Drug Rev 21:91-104. 2003The synthetic compound DX-9065a represents a low molecular weight, direct, competitive inhibitor of factor Xa (FXa) with a high affinity and selectivity for the enzyme...
In vitro inhibition of thrombin generation, after tissue factor pathway activation, by the oral, direct factor Xa inhibitor rivaroxabanG T Gerotziafas
J Thromb Haemost 5:886-8. 2007
Roles of coagulation pathway and factor Xa in rat mesangioproliferative glomerulonephritisKeiko Nomura
Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
Lab Invest 87:150-60. 2007Tissue 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...
Factor Xa stimulates fibroblast procollagen production, proliferation, and calcium signaling via PAR1 activationOlivier P Blanc-Brude
Royal Free and University College London Medical School, Centre for Cardiopulmonary Biochemistry and Respiratory Medicine, 5 University Street, London WC1E 6JJ, UK
Exp Cell Res 304:16-27. 2005..During hemostasis, the coagulation cascade proteinase factor X is converted into factor Xa. We have previously shown that factor Xa upregulates fibroblast proliferation via production of autocrine PDGF...
Design, synthesis, and biological activity of non-basic compounds as factor Xa inhibitors: SAR study of S1 and aryl binding sitesSatoshi 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...
Pentasaccharides in the prophylaxis and treatment of venous thromboembolism: a systematic reviewM Nijkeuter
Department of General Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands
Curr Opin Pulm Med 10:338-44. 2004..SUMMARY: Fondaparinux, one of the first of a new class of synthetic selective factor Xa inhibitors, is overall 50% more effective in reducing venous thromboembolism than enoxaparin in major orthopedic ..
Synthetic selective inhibitors of coagulation factor Xa strongly inhibit thrombin generation without affecting initial thrombin forming time necessary for platelet activation in hemostasisM Ieko
Departments of Internal Medicine, Health Sciences University of Hokkaido, Ishikari Tobetsu, Hokkaido, Japan
J Thromb Haemost 2:612-8. 2004....
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 inhibitorMimi 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. 2005Modification 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...
Assessment of three chromogenic and one clotting assays for the measurement of synthetic pentasaccharide fondaparinux (Arixtra) anti-Xa activityF Depasse
J Thromb Haemost 2:346-8. 2004
Virtual screening with flexible docking and COMBINE-based models. Application to a series of factor Xa inhibitorsMarta Murcia
Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York University, One Gustave Levy Place, Box 1218, New York, New York 10029, USA
J Med Chem 47:805-20. 2004..been successfully applied, as an example with medicinal chemistry interest, to a recently reported series of 133 factor Xa (fXa)(1) inhibitors whose activities encompass 4 orders of magnitude...
DX-9065a inhibits proinflammatory events induced by gingipains and factor XaKenji Matsushita
Department of Oral Disease Research, National Institute for Longevity Science, Aichi, Japan
J Periodontal Res 41:148-56. 2006..In this study, we investigated proinflammatory activities of Rgps and activated coagulation factor X (FXa) and examined the effect of DX-9065a, a new selective inhibitor of FXa, on proinflammatory events induced by these proteinases...
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 blooDonald J P Pinto
Discovery Chemistry Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543, USA
Bioorg Med Chem Lett 16:4141-7. 2006Attempts to further optimize the pyrazole factor Xa inhibitors centered on masking the aryl aniline P4 moiety...
Heparin derivatives as inhibitors of BACE-1, the Alzheimer's beta-secretase, with reduced activity against factor Xa and other proteasesSusannah 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...
Effect of vascular injury on inhibition of venous thrombosis with ZK-807834, a direct inhibitor of factor XaD R Abendschein
Center for Cardiovascular Research, Washington University School of Medicine, St Louis, MO 63110, USA
J Thromb Haemost 1:1955-8. 2003Inhibition of factor Xa with the small molecule inhibitor ZK-807834 (Mr 527 Da, Ki 0.11 nM) attenuates progression of thrombosis, but the ED50 is substantially lower for venous compared with arterial thrombosis in experimental animals...
First experience with direct, selective factor Xa inhibition in patients with non-ST-elevation acute coronary syndromes: results of the XaNADU-ACS TrialJ 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...
Inhibition of factor Xa suppresses the expression of tissue factor in human monocytes and lipopolysaccharide-induced endotoxemia in ratsK Akahane
Department of Surgery I, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Japan
Surgery 130:809-18. 2001..These results suggest that FXa is an important factor for TF expression in sepsis...
Antithrombotic and anticoagulant profiles of TAK-442, a novel factor Xa inhibitor, in a rabbit model of venous thrombosisMasaki Kawamura
Takeda Global Research and Development Center Inc, Deerfield, IL 60015, USA
J Cardiovasc Pharmacol 56:156-61. 2010The anticoagulant and antithrombotic profiles of TAK-442, a direct factor Xa (FXa) inhibitor, were investigated. TAK-442 showed potent inhibition of human FXa (Ki = 1...
Factor Xa induces tissue factor expression in endothelial cells by P44/42 MAPK and NF-κB-dependent pathwaysRong Jiang
Cardiothoracic Research Laboratory, Division of Cardiothoracic Surgery, Carlyle Fraser Heart Center, Emory University Hospital Midtown, Atlanta, Georgia, USA
J Surg Res 169:319-27. 2011Tissue factor (TF) is an initiator of coagulation. The serine protease factor Xa (FXa) is the convergence point of the extrinsic and intrinsic components of the coagulation cascade...
Coagulation factor Xa inhibition: biological background and rationaleR J Leadley
Pfizer Global Research and Development, Ann Arbor Laboratories, MI 48105, USA
Curr Top Med Chem 1:151-9. 2001..These agents, referred to as direct coagulation factor Xa inhibitors, appear to provide an enhanced risk-benefit margin compared to conventional therapy...
PRO_SELECT: combining structure-based drug design and array-based chemistry for rapid lead discovery. 2. The development of a series of highly potent and selective factor Xa inhibitorsJohn W Liebeschuetz
Protherics Molecular Design, Beechfield House, Lyme Green Business Park, Macclesfield SK11 0JL, UK
J Med Chem 45:1221-32. 2002..of libraries for fit to a protein active site, has been used to find novel leads against the serine protease factor Xa. A small seed template was built upon using three iterations of library design, virtual screening, synthesis, ..
Antithrombotic potential of GW813893: a novel, orally active, active-site directed factor Xa inhibitorMelanie A Abboud
GlaxoSmithKline, Cardiovascular and Urogenital Diseases Center of Excellence, King of Prussia, Pennsylvania, USA
J Cardiovasc Pharmacol 52:66-71. 2008b>Factor Xa (FXa) has been a target of considerable interest for drug development efforts aimed at suppressing thrombosis...
Achieving structural diversity using the perpendicular conformation of alpha-substituted phenylcyclopropanes to mimic the bioactive conformation of ortho-substituted biphenyl P4 moieties: discovery of novel, highly potent inhibitors of Factor XaJennifer X Qiao
Bristol Myers Squibb Company, Research and Development, PO Box 5400, Princeton, NJ 08543 5400, USA
Bioorg Med Chem Lett 18:4118-23. 2008..This is exemplified by the design and synthesis of a series of highly potent pyrazole bicyclic-based Factor Xa (FXa) inhibitors bearing alpha-substituted phenylcyclopropyl P4 moieties...
Coagulation signalling following tissue injury: focus on the role of factor XaMalvina 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...
Antithrombotic efficacy of a novel factor Xa inhibitor, FXV673, in a canine model of coronary artery thrombolysisS S Rebello
Cardiovascular Biology, Aventis Pharmaceuticals, Collegeville, Pennsylvania, U S A
Br J Pharmacol 133:1190-8. 2001We compared the antithrombotic efficacy of a potent factor Xa inhibitor, FXV673, to heparin and RPR109891, a GPIIb/IIIa antagonist, when used as adjunctive therapy in a canine model of rt-PA-induced coronary thrombolysis...
Fondaparinux, a synthetic pentasaccharide: the first in a new class of antithrombotic agents - the selective factor Xa inhibitorsKenneth A Bauer
VA Boston Health System, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA
Cardiovasc Drug Rev 20:37-52. 2002..agents developed for the prevention and treatment of VTE, inhibits thrombin generation by selectively inhibiting factor Xa. Fondaparinux exhibits complete bioavailability by the subcutaneous route and is rapidly absorbed, reaching its ..
Heparin enhances the inhibition of factor Xa by protein C inhibitor in the presence but not in the absence of Ca2+Wei Sun
Department of Medical Biochemistry and Microbiology, Uppsala University, Box 582, SE 751 23 Uppsala, Sweden
Biochemistry 48:1094-8. 2009..In this study, heparin was found to enhance PCI inhibition of factor Xa up to 42-fold in the presence of a physiological Ca(2+) concentration, whereas no heparin-induced activation was ..
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 inhibitorPenglie Zhang
Millennium Pharmaceuticals, Inc, South San Francisco, CA 94080, USA
Bioorg Med Chem Lett 19:2179-85. 2009Systematic SAR studies of in vitro factor Xa inhibitory activity around compound 1 were performed by modifying each of the three phenyl rings...
The discovery of the Factor Xa inhibitor otamixaban: from lead identification to clinical developmentKevin R Guertin
Department of Discovery Chemistry, Roche Research Center, 340 Kingsland St, Nutley, New Jersey 07110, USA
Curr Med Chem 14:2471-81. 2007b>Factor Xa (fXa) is a critical serine protease situated at the confluence of the intrinsic and extrinsic pathways of the blood coagulation cascade. FXa catalyses the conversion of prothrombin to thrombin via the prothrombinase complex...
Comparative metabolism of 14C-labeled apixaban in mice, rats, rabbits, dogs, and humansDonglu Zhang
Pharmaceutical Candidate Optimization, Bristol Myers Squibb Research and Development, Princeton, NJ 08543 4000, USA
Drug Metab Dispos 37:1738-48. 2009The metabolism and disposition of [(14)C]apixaban, a potent, reversible, and direct inhibitor of coagulation factor Xa, were investigated in mice, rats, rabbits, dogs, and humans after a single oral administration and in incubations with ..
Metabolism, pharmacokinetics and pharmacodynamics of the factor Xa inhibitor apixaban in rabbitsDonglu Zhang
Pharmaceutical Candidate Optimization, Bristol Myers Squibb Company, 311 Pennington Rocky Hill Road, Pennington, NJ 08534, USA
J Thromb Thrombolysis 29:70-80. 2010Apixaban has similar affinity for human and rabbit factor Xa (FXa)...
Inactivation of factor Xa by the synthetic inhibitor DX-9065a causes strong anticoagulant and antiplatelet actions in human bloodB Kaiser
Friedrich Schiller University Jena, Center for Vascular Biology and Medicine Erfurt, Germany
Blood Coagul Fibrinolysis 10:495-501. 1999In an in vitro study, anticoagulant and antiplatelet effects of the synthetic, direct factor Xa inhibitor DX-9065a, (+)-2S-2-[4-[[(3S)-1-acetimidoyl-3-pyrrolidinyl]oxy]phenyl]-3-[7-a midino-2-naphthyl]propanoic acid hydrochloride ..
Apixaban, a direct factor Xa inhibitor, inhibits tissue-factor induced human platelet aggregation in vitro: comparison with direct inhibitors of factor VIIa, XIa and thrombinPancras C Wong
Thrombosis Research, Bristol Myers Squibb Company, Pennington, New Jersey, USA
Thromb Haemost 104:302-10. 2010Apixaban is an oral, direct and highly selective factor Xa (FXa) inhibitor in late-stage clinical development...
Long-term anticoagulation: the prospects for alternatives to warfarinJack Ansell
Semin Vasc Surg 18:134-8. 2005..The low-molecular-weight heparins, and the indirect factor Xa inhibitor, fondaparinux, offer improvements, but both agents still need to be administered subcutaneously...
Changing trends in anti-coagulant therapies. Are heparins and oral anti-coagulants challenged?J Fareed
Hemostasis and Thrombosis Research Laboratoires, Loyola University Medical Center, Maywood, IL, USA
Int Angiol 27:176-92. 2008..Both the anti-factor Xa and anti-IIa agents have been developed for oral use and have provided impressive clinical results...
New anticoagulant strategies in ST elevation myocardial infarction: trials and clinical implicationsConor J McCann
Craigavon Cardiac Centre, Craigavon Area Hospital, Craigavon, Northern Ireland, UK
Vasc Health Risk Manag 4:305-13. 2008..current understanding of the underlying pathophysiology of STEMI and provides a comprehensive review of emerging trial data for low molecular weight heparins, anti-factor Xa agents and direct thrombin inhibitors in this setting.
Effect of oral contraceptives on the anticoagulant activity of protein S in plasmaRory R Koenen
Department of Biochemistry, Cardiovascular Research Institute Maastricht, The Netherlands
Thromb Haemost 93:853-9. 2005..Thrombin generation in the APC resistance assays was initiated either with factor Xa (Xa-APCsr) or tissue factor (TF-APCsr)...
Thrombin generation assays are superior to traditional tests in assessing anticoagulation reversal in vitroAlex Gatt
Sheffield Haemophilia and Thrombosis Centre, Royal Hallamshire Hospital, Sheffield, UK
Thromb Haemost 100:350-5. 2008..93 to 0.78 IU/ml. We conclude that the CAT is superior to the traditional coagulation tests in that it not only detects the coagulopathy of all the heparinoids but can be also be used to monitor their reversal...
Serpin-independent anticoagulant activity of a fucosylated chondroitin sulfateBianca F Glauser
Laboratório de Tecido Conjuntivo, Hospital Universitario Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Cidade Universitaria, Ilha do Fundao, Caixa Postal 68041, Rio de Janeiro, RJ, 21941 590, Brazil
Thromb Haemost 100:420-8. 2008..heparin, the invertebrate glycosaminoglycan is still able to prolong coagulation time and delay thrombin and factor Xa generation in serpin-free plasmas...
A preliminary assessment of the critical differences between novel oral anticoagulants currently in developmentBrian F McBride
Electrophysiologic and Metabolic Pharmacogenomics, Division of Clinical Pharmacology, Vanderbilt University School of Medicine, 536 Robinson Research Building, Nashville, TN 37232, USA
J Clin Pharmacol 45:1004-17. 2005..This review highlights the critical differences among oral anticoagulants in development and places their role in the context of the benefits and limitations of currently available anticoagulants...
Factor Xa inhibitors: new anti-thrombotic agents and their characteristicsMasahiro Ieko
Deaptment of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, Ishikari Tobetsu, Hokkaido, Japan
Front Biosci 11:232-48. 2006b>Factor Xa (FXa) is a key enzyme that is positioned at the convergence of the intrinsic and extrinsic pathways in the blood coagulation cascade, and inactivation by a specific FXa inhibitor effectively prevents the generation of thrombin...
Experimental study on anticoagulant and antiplatelet aggregation activity of a chemically sulfated marine polysaccharide YCPFang Han
School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, PR China
Int J Biol Macromol 36:201-7. 2005..absence of antithrombin III (AT III) or heparin cofactor II (HC II), while the derivates effectively inhibited factor Xa in the presence of AT III...
Blood coagulation-dependent inflammation. Coagulation-dependent inflammation and inflammation-dependent thrombosisSvetlana Strukova
Department of Human and Animal Physiology, Faculty of Biology, Lomonosov Moscow State University, Moscow, 119992, Russia
Front Biosci 11:59-80. 2006Hemostatic serine proteinases-thrombin, Factor VIIa, Factor Xa, play the central role in blood coagulation and thrombosis...
New anticoagulant drugs: a critical perspectiveSylvia Haas
Institute for Experimental Oncology and Therapy Research, Technical University Munich, Ismaninger Str. 22, 81675 Munich, Germany
Curr Hematol Rep 4:335-8. 2005
Assessment of the heparin-binding AN69 ST hemodialysis membrane: II. Clinical studies without heparin administrationSylvie Lavaud
, Centre Hospitalier et Universitaire and CNRS FRE 2534, Reims, France
ASAIO J 51:348-51. 2005..It is concluded that the dialysis AN69 ST membrane, after adequate priming at bedside, can be used without systemic administration of heparin for hemodialysis in patients at high risk of bleeding...
Differences in the clinically effective molar concentrations of four direct thrombin inhibitors explain their variable prothrombin time prolongationTheodore E Warkentin
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
Thromb Haemost 94:958-64. 2005..We compared the effects of these DTIs on various clotting assays and on inhibition of human and bovine factor Xa (FXa)...
Heparin and low-molecular-weight heparinElaine Gray
National Institute for Biological Standards and Control NIBSC, Blanche Lane, South Mimms, Potters Bar, Herts EN6 3QG, UK
Thromb Haemost 99:807-18. 2008..In this article the chemistry, mechanisms of action, measurement of anticoagulant activities, and clinical status of heparin and LMWH are reviewed...
The efficiency of anti-activated factor X and anti-activated factor II anticoagulantsThomas W Stief
Department of Clinical Chemistry, University Hospital Giessen and Marburg, Marburg, Germany
Blood Coagul Fibrinolysis 18:265-9. 2007..e. if about 0.1 IU/ml thrombin are inactivated, then thrombin cannot self-amplify its generation 10-fold). The efficiency of any clinically used plasmatic anticoagulant can be monitored in the EXCA...
Research Grants
- Dual Direct Inhibitors of Thrombin and Factor XaUmesh 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...
- Dual Direct Inhibitors of Thrombin and Factor XaUMESH 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...
- MOLECULAR BIOLOGY OF HUMAN COAGULATION FACTOR VWILLIAM KANE; Fiscal Year: 2009..The prothrombinase complex consists of the enzyme factor Xa, the cofactor factor Va and a phospholipid membrane surface...
- MOLECULAR BIOLOGY OF HUMAN COAGULATION FACTOR VThomas Ortel; Fiscal Year: 2010..The prothrombinase complex consists of the enzyme factor Xa, the cofactor factor Va and a phospholipid membrane surface...
- Lipid Regulation of Thrombin GenerationBarry 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...
- METAL DEPENDENT COMPLEXES IN BLOOD COAGULATIONBarbara 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...
- Lipid Regulation of Thrombin GenerationBarry 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...
- ANTIBODIES WITH PROTHROMBINASE ACTIVITY IN LUPUSPerumal Thiagarajan; Fiscal Year: 2003..g., antibody mediated inhibition of prothrombin activation by factor Xa; accelerated prothrombin clearance)...
- GLUCOSE TRANSPORTER STRUCTURE AND FUNCTIONAnthony 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...
- GLUCOSE TRANSPORTER STRUCTURE AND FUNCTIONAnthony 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...
- Tissue Factor Pathway Inhibitor Binding Proteins on EndoALAN MAST; Fiscal Year: 2005Tissue 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...
- FACTOR VA INTERACTIONS REGULATING PROTHROMBIN ACTIVATIONPaul 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...
- FACTOR VA INTERACTIONS REGULATING PROTHROMBIN ACTIVATIONPaul 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...
- MOLECULAR BIOLOGY OF HUMAN COAGULATION FACTOR VWILLIAM KANE; Fiscal Year: 2004..The prothrombinase complex consists of the enzyme factor Xa, the cofactor factor Va and a phospholipid membrane surface...
- Structural Mechanisms for the Inhibition of ThrombosisJAMES 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) ..
- Structural Mechanisms for the Inhibition of ThrombosisJAMES 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) ..
- MOLECULAR BIOLOGY OF HUMAN COAGULATION FACTOR VWILLIAM KANE; Fiscal Year: 2007..The prothrombinase complex consists of the enzyme factor Xa, the cofactor factor Va and a phospholipid membrane surface...
- MOLECULAR BIOLOGY OF HUMAN COAGULATION FACTOR VWILLIAM 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...
- Factor VIIIa interactions in the intrinsic factor XasePhilip 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 ..
- Protein interactions by analytical ultracentrifugationPETER 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)...
- PROTEINS OF COAGULATION PATHWAYSJohn H Griffin; Fiscal Year: 2010..we hypothesize that anticoagulant acyl carnitines, including palmitoyl carnitine, directly inhibit coagulation factor Xa by binding to Xa...
- Factor Vllla interactions in the intrinsic factor XasePhilip 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...
- BIOCHEMISTRY OF NORMAL & ABNORMAL VARIANTS OF FACTOR IXS 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 ..
- Thrombin Formation InhibitorsJames 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...
- Functional Domains of Coagulation Factor VMichael Kalafatis; Fiscal Year: 2007Prothrombinase 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...
- NMDA RECEPTOR FUNCTION BY SERINE PROTEASE RECEPTORSStephen 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 ..
- PROTEINS OF COAGULATION PATHWAYSJohn 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, ..
- AUTOIMMUNE MECHANISMS OF THROMBOSISRobert 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 ..
