Dual inhibition of HY023016 based on binding properties of platelet membrane receptor subunit glycoprotein Ibα and thrombin exosites.

Thrombin has long been suggested as a desirable antithrombotic target, but anti-thrombin therapy without anti-platelet thereby has never achieved the ideal effect. HY023016 is a novel compound, in our previous study, it exerted better anti-thrombotic than dabigatran etexilate. The present study aims to illustrate the excess anti-thrombotic molecular mechanisms of HY023016 through thrombin anion exosites and the platelet membrane receptor subunit glycoprotein Ibα (GPIbα).

Evaluating antithrombotic activity of HY023016 on rat hypercoagulable model.

The generation of thrombus is not considered as an isolated progression without other pathologic processes, which may also enhance procoagulant state. The purpose of this study was to assess whether HY023016, a novel dabigatran prodrug and an oral direct thrombin inhibitor, or dabigatran etexilate, another thrombin inhibitor can improve the state of whole blood hypercoagulability in vitro/vivo. By using whole blood flow cytometry we explored the effects of HY023016 and dabigatran etexilate on thrombin and ADP-induced human platelet-leukocyte aggregation generated in vitro.

Antithrombotic activity of HY023016, a novel Dabigatran prodrug evaluated in animal thrombosis models.

Introduction: Thrombin is a multifunctional trypsin-like serine protease that plays key roles in coagulation and thrombogenesis. HY023016, a novel Dabigatran prodrug, is an oral direct thrombin inhibitor. The purpose of this study was to compare the anti-thrombotic activities and haemorrhagic effects of HY023016 with Dabigatran etexilate and tetramethylpyrazine in several animal thrombosis models.