Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 61, Issue 9, Pages 3799-3822Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.7b00772
Keywords
-
Categories
Funding
- British Heart Foundation [SP/11/4/29251]
- British Heart Foundation [SP/11/4/29251] Funding Source: researchfish
Ask authors/readers for more resources
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 SIA proteases involved in coagulation and fibrinolysis is summarized.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available