血栓栓塞性疾病嚴(yán)重威脅人類健康，應(yīng)用抗血小板藥物是當(dāng)前主要的治療手段之一。研究證明，凝血酶受體（又稱蛋白酶激活受體-1，PAR-1）被凝血酶激活后，可誘導(dǎo)血小板活化。此外，PAR-1主要參與病理性血栓的形成，對人體正常的止血過程影響很小。因此，PAR-1已成為抗血小板藥物研發(fā)的新興靶點(diǎn)。目前，已有多個(gè)PAR-1拮抗劑如vorapaxar、F16618、F16357、ML161、RWJ-58259、PZ-128已上市或進(jìn)入臨床研究。綜述了PAR-1的結(jié)構(gòu)和作用機(jī)制以及小分子拮抗劑和多肽類拮抗劑的研究進(jìn)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, F16618, F16357, ML161, 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.