Schering-Plough Research Institute, 2015 Galloping Hill Rd, Kenilworth, NJ 07033, USA.
Expert Opin Ther Pat. 2006 Apr;16(4):493-505. doi: 10.1517/13543776.16.4.493.
In addition to its central role in haemostasis and wound healing, thrombin activates platelets and smooth muscle cells by proteolytic activation of cell surface protease-activated receptor-1 (PAR-1), which is also known as the thrombin receptor. Thrombin is the most potent activator of human platelets and, as such, a thrombin receptor antagonist is likely to exert potent antithrombotic effect in platelet-rich arterial thrombosis. As thrombin receptor antagonism does not inhibit the ability of thrombin to generate fibrin, such an agent is likely to have less bleeding liability than conventional anticoagulants. The proof-of-concept of the antithrombotic effect of PAR-1 antagonists has been established in several non-human primate models. The current success of PAR-1 research is underscored by the advancement of two candidates into clinical trails for acute coronary syndrome by Schering-Plough and Eisai Company.
除了在止血和伤口愈合中的核心作用外，凝血酶还通过蛋白水解激活细胞表面蛋白酶激活受体 1（PAR-1）来激活血小板和平滑肌细胞，PAR-1 也被称为凝血酶受体。凝血酶是人类血小板的最强激活剂，因此，凝血酶受体拮抗剂可能在富含血小板的动脉血栓形成中发挥强大的抗血栓作用。由于凝血酶受体拮抗作用不会抑制凝血酶生成纤维蛋白的能力，因此与传统抗凝剂相比，此类药物的出血风险可能较低。PAR-1 拮抗剂的抗血栓作用的概念验证已在几种非人类灵长类动物模型中得到证实。目前，Schering-Plough 和 Eisai 公司的两种候选药物在急性冠状动脉综合征的临床试验中的进展突显了 PAR-1 研究的成功。
