抗血栓新靶点PI3K的研究进展

Research Advances in Antithrombotic New Target of PI3K

随着人口老龄化程度的提高,血栓性疾病的发病率和死亡率也逐年增高,因而安全有效的抗血栓药物的开发成为目前药物研究领域的热点。血小板在血栓形成中具有非常重要的作用,但目前临床使用的抗血小板药物由于各方面的不足受到限制,尤其是出血副作用。磷脂酰肌醇3-激酶(Phosphatidylinositol 3-kinase,PI3K)是与细胞内信号转导相关的脂质激酶,在血小板活化的信号转导过程中发挥关键作用。目前正在研发的PI3Kβ抑制剂显示出良好的抑制血栓形成作用,同时不影响正常的止血过程,使PI3Kβ有望成为理想的抗血栓靶点。文章对PI3K的结构分类,血小板中的信号通路以及PI3K抑制剂作了综述。

Morbidity and mortality of thrombotic diseases are increasing year by year with an aging population, and therefore the development of safe and effective antithrombofic drugs becomes a research hotspot. Platelet plays an important role in thrombus formation ,but antiplatelet drugs in current clinical use are restricted due to various shortages, especially bleeding side effects. Phosphatidylinositol 3-kinase, a lipid kinase associated with intracellular signal transduction, plays a critical role in platelet activation. PI3Kβ inhibitors currently being developed show excellent antithrombotic effect,while not affecting normal hemostasis ,so PI3Kβ is expected to be an ideal antithrombofic target. This article focuses on the structure and classification of PI3K, platelet signaling pathways related to PI3K and PI3K inhibitors.