A Short Half-Life αIIbβ3 Antagonist ANTP266 Reduces Thrombus Formation

International Journal of Molecular Sciences

Shen-Hong Ren¹  Zhou-Ling Xie¹  Yi Kong²  Tong-Dan Liu²  Xue Ding² 

[1] Technology, China Pharmaceutical University, 24 Tong Jia Street, Nanjing 210009, China;;School of Life Science &

关键词: platelets;    bleeding risk;    antithrombosis;    αIIbβ3;    rapid elimination;   

DOI  :  10.3390/ijms19082306

来源: DOAJ

【 摘 要 】

Integrin αIIbβ3 plays a pivotal role in platelet aggregation. Three αIIbβ3 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 αIIbβ3 antagonist with low bleeding was needed. In the present study, we screened compounds by using a fibrinogen/integrin αIIbβ3 enzyme-linked immunosorbent assay (ELISA), and a novel αIIbβ3 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 αIIbβ3 antagonist of rapid elimination for a patient undergoing percutaneous coronary intervention.

【 授权许可】

Unknown