William A Schumacher

Summary

Affiliation: Bristol-Myers Squibb
Country: USA

Publications

  1. ncbi request reprint Biomarker optimization to track the antithrombotic and hemostatic effects of clopidogrel in rats
    William A Schumacher
    Bristol Myers Squibb Company, 311 Pennington Rocky Hill Road, Pennington, NJ 08534, USA
    J Pharmacol Exp Ther 322:369-77. 2007
  2. ncbi request reprint Antithrombotic and hemostatic effects of a small molecule factor XIa inhibitor in rats
    William A Schumacher
    Discovery Biology, Bristol Myers Squibb Company, Pennington, New Jersey 08534, USA
    Eur J Pharmacol 570:167-74. 2007
  3. doi request reprint Effect of the direct factor Xa inhibitor apixaban in rat models of thrombosis and hemostasis
    William A Schumacher
    Thrombosis Biology, Bristol Myers Squibb Company, Pennington, NJ 08534 2130, USA
    J Cardiovasc Pharmacol 55:609-16. 2010
  4. ncbi request reprint Clopidogrel versus prasugrel in rabbits. Effects on thrombosis, haemostasis, platelet function and response variability
    Pancras C Wong
    Thrombosis Research, Bristol Mayers, Squibb Company, Pennington, NJ 08534, USA
    Thromb Haemost 101:108-15. 2009
  5. ncbi request reprint Platelet aggregometry and receptor binding to predict the magnitude of antithrombotic and bleeding time effects of clopidogrel in rabbits
    Pancras C Wong
    Discovery Biology, Bristol Myers Squibb Company, Pennington, New Jersey 08534, USA
    J Cardiovasc Pharmacol 49:316-24. 2007
  6. doi request reprint A platelet target for venous thrombosis? P2Y1 deletion or antagonism protects mice from vena cava thrombosis
    J Eileen Bird
    Department of Thrombosis Biology, Bristol Myers Squibb, 311 Pennington Rocky Hill Road, Pennington, NJ 08534, USA
    J Thromb Thrombolysis 34:199-207. 2012
  7. doi request reprint Effects of plasma kallikrein deficiency on haemostasis and thrombosis in mice: murine ortholog of the Fletcher trait
    J Eileen Bird
    Department of Thrombosis Biology, Bristol Myers Squibb, Pennington, New Jersey 08534, USA
    Thromb Haemost 107:1141-50. 2012
  8. doi request reprint A small-molecule factor XIa inhibitor produces antithrombotic efficacy with minimal bleeding time prolongation in rabbits
    Pancras C Wong
    Cardiovascular Biology, Bristol Myers Squibb Company, 311 Pennington Rocky Hill Road, Pennington, NJ 08534, USA
    J Thromb Thrombolysis 32:129-37. 2011
  9. ncbi request reprint Deficiency in thrombin-activatable fibrinolysis inhibitor (TAFI) protected mice from ferric chloride-induced vena cava thrombosis
    Xinkang Wang
    Department of Thrombosis Biology, Bristol Myers Squibb Company, 311 Pennington Rocky Hill Road, Pennington, NJ 08534, USA
    J Thromb Thrombolysis 23:41-9. 2007
  10. doi request reprint Inhibition of factor XIa as a new approach to anticoagulation
    William A Schumacher
    Bristol Myers Squibb, Hopewell Biology Drug Discovery, 311 Pennington Rocky Hill Rd, Pennington, NJ 08534, USA
    Arterioscler Thromb Vasc Biol 30:388-92. 2010

Collaborators

Detail Information

Publications27

  1. ncbi request reprint Biomarker optimization to track the antithrombotic and hemostatic effects of clopidogrel in rats
    William A Schumacher
    Bristol Myers Squibb Company, 311 Pennington Rocky Hill Road, Pennington, NJ 08534, USA
    J Pharmacol Exp Ther 322:369-77. 2007
    ..In summary, antithrombotic doses of clopidogrel have limited effects on bleeding and standard measures of platelet aggregation. Other biomarkers may be more sensitive for tracking antithrombotic efficacy...
  2. ncbi request reprint Antithrombotic and hemostatic effects of a small molecule factor XIa inhibitor in rats
    William A Schumacher
    Discovery Biology, Bristol Myers Squibb Company, Pennington, New Jersey 08534, USA
    Eur J Pharmacol 570:167-74. 2007
    ..These results demonstrate that pharmacologic inhibition of factor XIa achieves antithrombotic efficacy with minimal effects on provoked bleeding...
  3. doi request reprint Effect of the direct factor Xa inhibitor apixaban in rat models of thrombosis and hemostasis
    William A Schumacher
    Thrombosis Biology, Bristol Myers Squibb Company, Pennington, NJ 08534 2130, USA
    J Cardiovasc Pharmacol 55:609-16. 2010
    ..In summary, apixaban was effective in a broad range of thrombosis models at doses producing modest increases in multiple bleeding time models...
  4. ncbi request reprint Clopidogrel versus prasugrel in rabbits. Effects on thrombosis, haemostasis, platelet function and response variability
    Pancras C Wong
    Thrombosis Research, Bristol Mayers, Squibb Company, Pennington, NJ 08534, USA
    Thromb Haemost 101:108-15. 2009
    ..3-7 times less potent than prasugrel in rabbits, depending upon which biomarker was studied. The ratio of efficacy: bleeding was most favorable at a moderate IPA of 30% to 40%. Both compounds had similar IPA and RO response variability...
  5. ncbi request reprint Platelet aggregometry and receptor binding to predict the magnitude of antithrombotic and bleeding time effects of clopidogrel in rabbits
    Pancras C Wong
    Discovery Biology, Bristol Myers Squibb Company, Pennington, New Jersey 08534, USA
    J Cardiovasc Pharmacol 49:316-24. 2007
    ..Moreover, modified IPA and P2Y12 receptor occupancy appear to better predict the magnitude of clopidogrel's efficacy compared with standard IPA, which may be a better predictor of BT...
  6. doi request reprint A platelet target for venous thrombosis? P2Y1 deletion or antagonism protects mice from vena cava thrombosis
    J Eileen Bird
    Department of Thrombosis Biology, Bristol Myers Squibb, 311 Pennington Rocky Hill Road, Pennington, NJ 08534, USA
    J Thromb Thrombolysis 34:199-207. 2012
    ..However as with many antithrombotic agents the benefit comes at the potential price of an increase in provoked bleeding times...
  7. doi request reprint Effects of plasma kallikrein deficiency on haemostasis and thrombosis in mice: murine ortholog of the Fletcher trait
    J Eileen Bird
    Department of Thrombosis Biology, Bristol Myers Squibb, Pennington, New Jersey 08534, USA
    Thromb Haemost 107:1141-50. 2012
    ..Additional support for the significance of the intrinsic pathway in the coagulation cascade is provided, as well as for a potential new anti-thrombotic approach...
  8. doi request reprint A small-molecule factor XIa inhibitor produces antithrombotic efficacy with minimal bleeding time prolongation in rabbits
    Pancras C Wong
    Cardiovascular Biology, Bristol Myers Squibb Company, 311 Pennington Rocky Hill Road, Pennington, NJ 08534, USA
    J Thromb Thrombolysis 32:129-37. 2011
    ..05 vs. control). This study demonstrated that BMS-262084 prevented experimental thrombosis at doses with low BT effects in rabbits, and suggests that a small molecule FXIa inhibitor may represent a promising antithrombotic therapy...
  9. ncbi request reprint Deficiency in thrombin-activatable fibrinolysis inhibitor (TAFI) protected mice from ferric chloride-induced vena cava thrombosis
    Xinkang Wang
    Department of Thrombosis Biology, Bristol Myers Squibb Company, 311 Pennington Rocky Hill Road, Pennington, NJ 08534, USA
    J Thromb Thrombolysis 23:41-9. 2007
    ..The strong ex vivo fibrinolytic activity of TAFI deficiency or TAFIa inhibition by PCI provides a biomarker of TAFIa inhibition that tracks in vivo antithrombotic efficacy...
  10. doi request reprint Inhibition of factor XIa as a new approach to anticoagulation
    William A Schumacher
    Bristol Myers Squibb, Hopewell Biology Drug Discovery, 311 Pennington Rocky Hill Rd, Pennington, NJ 08534, USA
    Arterioscler Thromb Vasc Biol 30:388-92. 2010
    ..Together, these data strongly support FXIa inhibition as a viable method to increase the ratio of benefit to risk in an antithrombotic drug...
  11. doi request reprint In vitro, antithrombotic and bleeding time studies of BMS-654457, a small-molecule, reversible and direct inhibitor of factor XIa
    Pancras C Wong
    Cardiovascular Drug Discovery Biology, Bristol Myers Squibb Company, 311 Pennington Rocky Hill Road, Pennington, NJ, 08534, USA
    J Thromb Thrombolysis 40:416-23. 2015
    ..This study supports inhibition of FXIa, with a small-molecule, reversible and direct inhibitor as a promising antithrombotic therapy with a wide therapeutic window. ..
  12. doi request reprint Blockade of protease-activated receptor-4 (PAR4) provides robust antithrombotic activity with low bleeding
    Pancras C Wong
    Bristol Myers Squibb Company, 311 Pennington Rocky Hill Road, Pennington, NJ 08534, USA
    Sci Transl Med 9:. 2017
    ..In addition, they indicate that targeting PAR4 is an attractive antiplatelet strategy with the potential to treat patients at a high risk of atherothrombosis with superior safety compared with the current standard of care...
  13. doi request reprint Discovery of diarylurea P2Y(1) antagonists with improved aqueous solubility
    Tammy C Wang
    Medicinal Chemistry, Molecular Sciences and Candidate Optimization, Bristol Myers Squibb, 311 Pennington Rocky Hill Road, Pennington, NJ 08534, USA
    Bioorg Med Chem Lett 23:3239-43. 2013
    ..Compound 2l was moderately efficacious in both rat and rabbit thrombosis models and had a moderate prolongation of bleeding time in rats similar to that of compound 1...
  14. doi request reprint Conformationally constrained ortho-anilino diaryl ureas: discovery of 1-(2-(1'-neopentylspiro[indoline-3,4'-piperidine]-1-yl)phenyl)-3-(4-(trifluoromethoxy)phenyl)urea, a potent, selective, and bioavailable P2Y1 antagonist
    Jennifer X Qiao
    Research and Development, Bristol Myers Squibb Company, 311 Pennington Rocky Hill Road, Pennington, New Jersey 08534, United States
    J Med Chem 56:9275-95. 2013
    ..Compound 3l was our first P2Y1 antagonist to demonstrate a robust oral antithrombotic effect with mild bleeding liability in the rat thrombosis and hemostasis models. ..
  15. doi request reprint Identification of 1-{2-[4-chloro-1'-(2,2-dimethylpropyl)-7-hydroxy-1,2-dihydrospiro[indole-3,4'-piperidine]-1-yl]phenyl}-3-{5-chloro-[1,3]thiazolo[5,4-b]pyridin-2-yl}urea, a potent, efficacious and orally bioavailable P2Y(1) antagonist as an antiplatelet
    Yoon T Jeon
    Discovery Chemistry, Bristol Myers Squibb, 311 Pennington Rocky Hill Road, Pennington, NJ 08534, USA
    Bioorg Med Chem Lett 24:1294-8. 2014
    ..Compound 3e demonstrated a robust antithrombotic effect in vivo and improved bleeding risk profile compared to the P2Y12 antagonist clopidogrel in rat efficacy/bleeding models. ..
  16. doi request reprint Aroylguanidine-based factor Xa inhibitors: the discovery of BMS-344577
    Yan Shi
    Research and Development, Bristol Myers Squibb Company, PO Box 5400, Princeton, NJ 08543 5400, USA
    Bioorg Med Chem Lett 19:6882-9. 2009
    ..5 microM), which was found to be a selective, orally efficacious FXa inhibitor with an excellent in vitro liability profile, favorable pharmacokinetics and pharmacodynamics in animal models...
  17. doi request reprint Cyanoguanidine-based lactam derivatives as a novel class of orally bioavailable factor Xa inhibitors
    Yan Shi
    Research and Development, Bristol Myers Squibb Company, PO Box 5400, Princeton, NJ 08543 5400, USA
    Bioorg Med Chem Lett 19:4034-41. 2009
    ..The X-ray crystal structure of 4 bound in FXa is presented and key ligand-protein interactions are discussed...
  18. ncbi request reprint Molecular design and structure--activity relationships leading to the potent, selective, and orally active thrombin active site inhibitor BMS-189664
    Jagabandhu Das
    Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543 4000, USA
    Bioorg Med Chem Lett 12:45-9. 2002
    ....
  19. ncbi request reprint Synthesis and SAR of 4-carboxy-2-azetidinone mechanism-based tryptase inhibitors
    James C Sutton
    The Bristol Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543 4000, USA
    Bioorg Med Chem Lett 12:3229-33. 2002
    ....
  20. ncbi request reprint Synthesis of potent and highly selective inhibitors of human tryptase
    William A Slusarchyk
    The Bristol Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543 4000, USA
    Bioorg Med Chem Lett 12:3235-8. 2002
    ..7 nM) with high selectivity (>3000-fold) for tryptase versus related serine proteases including trypsin...
  21. ncbi request reprint Inhibition of tumor necrosis factor-alpha-converting enzyme by a selective antagonist protects brain from focal ischemic injury in rats
    Xinkang Wang
    Department of Thrombosis Research, Bristol Myers Squibb Company, P O Box 5400, Princeton, NJ 08543 5400, USA
    Mol Pharmacol 65:890-6. 2004
    ..Our data suggest that inhibition of TACE might be a potential therapeutic strategy for neuroprotection after focal ischemic stroke...
  22. ncbi request reprint Ketene aminal-based lactam derivatives as a novel class of orally active FXa inhibitors
    Yan Shi
    Bristol Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543 5400, USA
    Bioorg Med Chem Lett 15:5453-8. 2005
    ..N,N'-Disubstituted ketene aminals are good bioisosteres of thiourea functional groups. We report the design and synthesis of a novel class of ketene aminal-based lactam derivatives as potent and orally active FXa inhibitors...
  23. ncbi request reprint Is exogenous tissue plasminogen activator necessary for antithrombotic efficacy of an inhibitor of thrombin activatable fibrinolysis inhibitor (TAFI) in rats?
    Eileen Bird
    Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey, 08543, United States
    Thromb Res 120:549-58. 2007
    ..This study was designed to further explore the importance of exogenous tPA in revealing PCI activity in rat models of venous and arterial thrombosis and provoked bleeding...
  24. doi request reprint Prediction of the therapeutic index of marketed anti-coagulants and anti-platelet agents by guinea pig models of thrombosis and hemostasis
    J Eileen Bird
    Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543, USA
    Thromb Res 123:146-58. 2008
    ..The goal of the current study was to benchmark representative marketed drugs in thrombosis and hemostasis models in guinea pigs...
  25. doi request reprint Design, structure-activity relationships, X-ray crystal structure, and energetic contributions of a critical P1 pharmacophore: 3-chloroindole-7-yl-based factor Xa inhibitors
    Yan Shi
    Bristol Myers Squibb Research and Development, P O Box 5400, Princeton, New Jersey 08543 5400, USA
    J Med Chem 51:7541-51. 2008
    ..The stronger hydrophobicity of chloro- versus methyl-substituted aromatics may partly explain the general preference for chloro- versus methyl-substituted P1 groups in FXa, which extends beyond the current series...
  26. ncbi request reprint Thrombin active site inhibitors: chemical synthesis, in vitro and in vivo pharmacological profile of a novel and selective agent BMS-189090 and analogues
    Jagabandhu Das
    Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543 4000, USA
    Bioorg Med Chem Lett 12:41-4. 2002
    ..BMS-189090 (5) is identified as a potent, selective, and reversible inhibitor of human alpha-thrombin that is efficacious in vivo in a mice lethality model, and in inhibiting both arterial and venous thrombosis in a rat model...
  27. ncbi request reprint Quantification of platelet composition in experimental venous thrombosis by real-time polymerase chain reaction
    Xinkang Wang
    Department of Thrombosis Biology, Bristol Myers Squibb Company, Pennington, NJ 08534, USA
    Thromb Res 119:593-600. 2007
    ..In this study a sensitive and reliable method to characterize the cellular components of experimental thrombi was developed using real-time polymerase chain reaction (PCR)...