Discovery methods of coagulation-inhibiting drugs

Introduction: In the last decade, several direct oral anticoagulants (DOAC) targeting thrombin (dabigatran) or activated factor X (FXa) (rivaroxaban, apixaban and edoxaban) have been marketed for a number of indications related to prophylaxis and treatment of thrombotic diseases. All these drugs are effective in preventing thrombosis, but are associated with an increased bleeding risk.

Areas covered: This review includes a summary of new targets for anticoagulation (e.g.: FXIa, FXIIa, protein disulfide isomerase, polyphosphates, etc.), the discovery process and pharmacological features of new anticoagulant compounds and the available results from non-clinical and clinical studies. A significant number of new anticoagulant compounds are currently in development. These compounds were developed using different technologies like SELEX (aptamers), antisense technology (ASOs), hybridoma (MAB) and structure based drug design. Compounds like ichorcumab (a parenteral thrombin inhibitor), BMS-986177 (oral FXIa inhibitor), BAY-1213790 and xisomab (parenteral FXIa inhibitors) are currently in the clinical development stage.

Expert opinion: It’s important to be cautious when interpreting preliminary findings of new compounds showing a good antithrombotic effect without altering haemostasis. That being said, the anticoagulants in development have the potential to provide a safer alternative to the currently available anticoagulants in patients at high risk of bleeding, but further investigation is warranted.