Peter M. Fischer
Design of small-molecule active-site inhibitors of the S1A family proteases as procoagulant and anticoagulant drugs
Fischer, Peter M.
Vitamin K antagonists (VKA) have long been the default drugs for anticoagulant management in venous thrombosis. While efficacious, they are difficult to use due to interpatient dose–response variability and the risks of bleeding. The approval of fondaparinux, a heparin-derived factor Xa (fXa) inhibitor, provided validation for the development of direct oral anticoagulants (DOAC), and currently such inhibitors of thrombin and fXa are in clinical use. These agents can be used without regular coagulation monitoring, but the inherent risk of bleeding complications associated with blocking the common coagulation pathway remains. Efforts are now underway to develop DOACs that inhibit components of the intrinsic and extrinsic coagulation cascades upstream of thrombin and fX. Evidence from humans and from transgenic animal models suggests that this strategy may provide a better therapeutic margin between antithrombotic and antihemostatic effects. Here the design of active-site inhibitors of S1A proteases involved in coagulation and fibrinolysis is summarized.
|Journal Article Type||Article|
|Journal||Journal of Medicinal Chemistry|
|Publisher||American Chemical Society|
|Peer Reviewed||Peer Reviewed|
|APA6 Citation||Fischer, P. M. (in press). Design of small-molecule active-site inhibitors of the S1A family proteases as procoagulant and anticoagulant drugs. Journal of Medicinal Chemistry, 61(9), https://doi.org/10.1021/acs.jmedchem.7b00772|
|Copyright Statement||Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0|
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0