Trends in Pharmacological Sciences ( IF 13.9 ) Pub Date : 2017-08-29 , DOI: 10.1016/j.tips.2017.08.001 Benjamin E. Tourdot , Michael Holinstat
Platelets are key contributors to the formation of occlusive thrombi; the major underlying cause of ischemic heart disease and stroke. Antiplatelet therapy has reduced the morbidity and mortality associated with thrombotic events; however, the utility of current antiplatelet therapies is limited by the concomitant risk of an adverse bleeding event. Novel antiplatelet therapies that are more efficacious at inhibiting thrombosis while minimally affecting hemostasis are required. Platelet-type 12-(S)-lipoxygenase (12-LOX), an oxygenase shown to potentiate platelet activation, represents a novel antiplatelet target. Recently, a selective 12-LOX inhibitor, ML355, was shown to decrease thrombosis without prolonging hemostasis. While published data suggests targeting 12-LOX is a viable approach, further work is required to determine the safety and effectiveness of 12-LOX inhibitors in humans.
中文翻译:
靶向12-Lipoxygenase作为潜在的新型抗血小板治疗
血小板是闭塞性血栓形成的关键因素。缺血性心脏病和中风的主要原因。抗血小板治疗降低了与血栓形成事件相关的发病率和死亡率。然而,目前的抗血小板疗法的实用性受到伴随的不良出血事件风险的限制。需要在抑制血栓形成同时最小限度地影响止血方面更有效的新型抗血小板疗法。血小板型12-(S)-脂加氧酶(12-LOX)是一种能增强血小板活化作用的加氧酶,代表一种新型的抗血小板靶标。最近,选择性的12-LOX抑制剂ML355被证明可以减少血栓形成而不会延长止血时间。尽管公开的数据表明靶向12-LOX是一种可行的方法,但仍需要进一步的工作来确定12-LOX抑制剂在人体中的安全性和有效性。