[Concepts in anticoagulant therapy - past, present, and future]

Area of Science:

• Pharmacology
• Hematology
• Drug Discovery

Background:

• Anticoagulant development has evolved from serendipitous discovery to targeted drug design.
• The cell-based model of hemostasis highlights the critical roles of clotting factors Xa (FXa) and thrombin.
• Vitamin K-antagonists and heparins represent earlier anticoagulant classes.

Purpose of the Study:

• To review the development and targets of modern anticoagulants.
• To discuss the significance of FXa and thrombin as targets for anticoagulation.
• To outline emerging anticoagulant strategies and their developmental stages.

Main Methods:

• Review of scientific literature on anticoagulant development.
• Analysis of the mechanism of action for various anticoagulant classes.
• Categorization of anticoagulants based on their targets and developmental phase.

Main Results:

• Direct FXa inhibitors (rivaroxaban, apixaban, edoxaban) and direct thrombin inhibitors (dabigatran etexilate) are now licensed oral anticoagulants.
• Several FXa and thrombin inhibitors with modified pharmacokinetics are in advanced development.
• Inhibition of factor VIII represents a new clinical-stage anticoagulation concept, with other targets like factor VIIa, XII, and IX in early development.

Conclusions:

• Targeted inhibition of FXa and thrombin has been successfully translated into effective anticoagulants.
• Ongoing research is exploring novel targets and drug candidates to expand anticoagulation options.
• The field is moving towards more specific and potentially safer anticoagulant therapies.