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Integrin α IIb β₃ plays a pivotal role in platelet aggregation. Three α IIb β₃ antagonists have been approved by the Food and Drug Administration (FDA) for the treatment of cardiovascular diseases. Unfortunately, all of these three drugs can cause the side effect of severe bleeding. Therefore, developing a new α IIb β₃ antagonist with low bleeding was needed. In the present study, we screened compounds by using a fibrinogen/integrin α IIb β₃ enzyme-linked immunosorbent assay (ELISA), and a novel α IIb β₃ antagonist ANTP266 was attained. The antithrombotic effects of ANTP266 were estimated by using two animal models, the bleeding risk was estimated by using a mice tail cutting assay, and the plasma half-life time was tested by LC-MS/MS. The results showed that ANTP266 potently decreased thrombosis formation, while not prolonging bleeding time at its effective dosage. The bleeding of ANTP266 reduced rapidly as time went on from 5 to 60 min, but tirofiban produced high bleeding continuously. The plasma half-life of ANTP266 in rats was 10.8 min. Taken together, ANTP266 is an effective antithrombotic agent with a low bleeding risk. The shorter bleeding time benefits from its short plasma half-life. ANTP266 could be a candidate for developing the α IIb β₃ antagonist of rapid elimination for a patient undergoing percutaneous coronary intervention.

A Short Half-Life αIIbβ3 Antagonist ANTP266 Reduces Thrombus Formation