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Progress in the development of antiplatelet agents: Focus on the targeted molecular pathway from bench to clinic.
Pharmacology & Therapeutics ( IF 12.0 ) Pub Date : 2019-07-26 , DOI: 10.1016/j.pharmthera.2019.107393
Qian Xiang 1 , Xiaocong Pang 1 , Zhenming Liu 2 , Guoping Yang 3 , Weikang Tao 3 , Qi Pei 4 , Yimin Cui 1
Affiliation  

Antiplatelet drugs serve as a first-line antithrombotic therapy for the management of acute ischemic events and the prevention of secondary complications in vascular diseases. Numerous antiplatelet therapies have been developed; however, currently available agents are still associated with inadequate efficacy, risk of bleeding, and variability in individual response. Understanding the mechanisms of platelet involvement in thrombosis and the clinical development process of antiplatelet agents is critical for the discovery of novel agents. The functions of platelets in thrombosis are regulated by two major mechanisms: the interaction between surface receptors and their ligands, and the downstream intracellular signaling pathways. Recently, most of the progress made in antiplatelet drug development has been achieved with P2Y receptor antagonists. Additionally, the usage of GP IIb/IIIa receptor antagonists has decreased, because it is associated with a higher risk of bleeding and thrombocytopenia. Agents targeting other platelet surface receptors such as PARs, TP receptor, EP3 receptor, GPIb-IX-V receptor, P-selectin, as well as intracellular signaling factors, such as PI3Kβ, have been evaluated in an attempt to develop the next generation of antiplatelet drugs, reduce or eliminate interpatient variability of drug efficacy and significantly lower the risk of drug-induced bleeding. The aim of this review is to describe the pathways of platelet activation in thrombosis, and summarize the development process of antiplatelet agents, as well as the preclinical and clinical evaluations performed on these agents.

中文翻译:

抗血小板药物开发的进展:专注于从实验台到临床的靶向分子途径。

抗血小板药物是一线抗血栓治疗,用于管理急性缺血事件和预防血管疾病的继发性并发症。已经开发出了许多抗血小板疗法。然而,目前可用的药物仍然与功效不足,出血风险和个体反应的变异性有关。了解血小板参与血栓形成的机制和抗血小板药物的临床开发过程对于发现新型药物至关重要。血小板在血栓形成中的功能受两个主要机制调控:表面受体及其配体之间的相互作用以及下游的细胞内信号传导途径。最近,使用P2Y受体拮抗剂已取得了抗血小板药物开发的大部分进展。另外,GP IIb / IIIa受体拮抗剂的使用有所减少,因为它与出血和血小板减少症的较高风险相关。已经评估了靶向其他血小板表面受体(例如PARs,TP受体,EP3受体,GPIb-IX-V受体,P-选择素)以及细胞内信号传导因子(例如PI3Kβ)的药物,以尝试开发下一代的抗血小板药物,减少或消除患者间药物疗效的差异,并显着降低药物引起的出血的风险。这篇综述的目的是描述血栓形成中血小板活化的途径,并概述抗血小板药物的开发过程,以及对这些药物进行的临床前和临床评估。因为它与出血和血小板减少的风险较高有关。已经评估了靶向其他血小板表面受体(例如PARs,TP受体,EP3受体,GPIb-IX-V受体,P-选择素)以及细胞内信号传导因子(例如PI3Kβ)的药物,以尝试开发下一代的抗血小板药物,减少或消除患者间药物疗效的差异,并显着降低药物引起的出血的风险。这篇综述的目的是描述血栓形成中血小板活化的途径,并概述抗血小板药物的开发过程,以及对这些药物进行的临床前和临床评估。因为它与出血和血小板减少的风险较高有关。已经评估了靶向其他血小板表面受体(例如PARs,TP受体,EP3受体,GPIb-IX-V受体,P-选择素)以及细胞内信号传导因子(例如PI3Kβ)的药物,以尝试开发下一代的抗血小板药物,减少或消除患者间药物疗效的差异,并显着降低药物引起的出血的风险。这篇综述的目的是描述血栓形成中血小板活化的途径,并概述抗血小板药物的开发过程,以及对这些药物进行的临床前和临床评估。已评估了GPIb-IX-V受体,P-选择素以及细胞内信号传导因子(例如PI3Kβ),以尝试开发下一代抗血小板药物,减少或消除患者间药物疗效的差异并显着降低风险药物引起的出血。这篇综述的目的是描述血栓形成中血小板活化的途径,并概述抗血小板药物的开发过程,以及对这些药物进行的临床前和临床评估。已评估了GPIb-IX-V受体,P-选择素以及细胞内信号传导因子(例如PI3Kβ),以尝试开发下一代抗血小板药物,减少或消除患者间药物疗效的差异并显着降低风险药物引起的出血。这篇综述的目的是描述血栓形成中血小板活化的途径,并概述抗血小板药物的开发过程,以及对这些药物进行的临床前和临床评估。
更新日期:2019-11-18
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