凝血酶受体拮抗剂的研究进展

Research progress on thrombin receptorantagonists

血栓栓塞性疾病严重威胁人类健康,应用抗血小板药物是当前主要的治疗手段之一。研究证明,凝血酶受体(又称蛋白酶激活受体-1,PAR-1)被凝血酶激活后,可诱导血小板活化。此外,PAR-1主要参与病理性血栓的形成,对人体正常的止血过程影响很小。因此,PAR-1已成为抗血小板药物研发的新兴靶点。目前,已有多个PAR-1拮抗剂如vorapaxar、F16618、F16357、ML161、RWJ-58259、PZ-128已上市或进入临床研究。综述了PAR-1的结构和作用机制以及小分子拮抗剂和多肽类拮抗剂的研究进展。

Thromboembolic disease threatened human health seriously, and the antiplatelet therapy is one of the most important strategies. Protease-activated receptor （PAR）-1, which is activated by thrombin, represents a novel promising approach in the treatment of atherothrombotic disease. Moreover, PAR-1 inhibition has been proved exerts little effect on physiological hemostasis, but on pathological thrombus formation. So far, several PAR- 1 antagonists such as vorapaxar, F 16618, F 16357, ML 161, RWJ-58259, and PZ-128 have been reported. This paper reviews the progress in the study of structure and mechanism of PAR-1 as well as the development of Small molecular and peptides PAR-1 antagonists.