蛋白酶激活受体拮抗剂在抗血小板领域的研究进展

Research progress on protease-activated receptor antagonists in the field of antiplatelet

蛋白酶激活受体(protease activated receptors,PARs)是G蛋白偶联受体的家族成员之一。研究发现蛋白酶激活受体可经凝血酶激活诱导血小板的聚集,参与血栓形成过程。人类血小板主要表达蛋白酶激活受体-1和蛋白酶激活受体-4两种受体,因此蛋白酶激活受体-1和蛋白酶激活受体-4可作为抗血小板药物的新靶点。本文介绍了凝血酶诱导蛋白酶激活受体-1、蛋白酶激活受体-4活化的作用机制,并对近年来蛋白酶激活受体-1和蛋白酶激活受体-4小分子拮抗剂的结构、药理活性的研究进展进行总结。

Protease-activated receptors(PARs)are members of G-protein coupled receptors.In recent years,researchers have found that PARs can induce platelet aggregation via thrombin activation and participate in the thrombosis process.Human platelets mainly express PAR-1 and PAR-4,which may serve as new targets for antiplatelet drugs.This article summarized mechanism of thrombin-induced PAR-1 and PAR-4 activation,and advances in research on structure and pharmacological activities of small molecule antagonists of PAR-1 and PAR-4 were also reviewed.