Novel selective anti-platelet and clot-specific anticoagulant strategies targeting conformational states of GPIIb/IIIa

抑制血小板和抑制凝血因子是医学上应用最广泛的药物之一，为许多患者提供了重大好处。预防和治疗血栓形成、血栓、中风和心脏病发作是使用抗血小板和抗凝血药的许多疾病的例子。然而，这些药物的缺点是出血并发症，可能导致死亡或残疾。这些与药物有关的出血并发症的后果也是我们医疗保健系统的主要财务负担。因此，在出血并发症较少的治疗策略方面取得进展是非常受欢迎的。这项拟议的项目旨在产生新的基于抗体的抑制血小板的药物。其中一组药物只在血小板被激活时才会阻断它们。此外，这些药物允许凝血因子的有效抑制物在血栓部位浓缩。因此，这些抑制剂应该主要作用于需要它们的部位。同时，凝血因子抑制物的总浓度可以保持在较低水平，未激活的血小板功能可以保持不变。总体而言，拟议的项目旨在开发具有高抗血栓疗效和低出血风险的新的抗血小板和抗凝血剂策略。

The inhibition of platelets and the inhibition of coagulation factors are among the most widely used drugs in medicine and provide major benefits for numerous patients. Prevention and treatment of thrombosis, emboli, stroke and heart attack are examples of the many diseases where anti-platelet and anticoagulant drugs are administered. However, the downsides of these drugs are bleeding complications, which can result in death or disability. The consequences of these drug-associated bleeding complications are also a major financal burden for our health care system. Thus, progress towards therapeutic strategies with less bleeding complications is highly sought-after. The proposed project aims to generate new antibody-based agents for platelet inhibition. One group of these agents do only block platelets when they are activated. Furthermore, these agents allow an enrichment of potent inhibitors of coagulation factors at the site of the clot. Thus, these inhibitors should predominatly act at the site where they are needed. At the same time the overall concentration of inhibitors of coagulation factors can be kept low and the functions of non-activated platelet can be left intact. Overall, the proposed project aims for the development of novel anti-platelet and anticoagulant strategies with high anti-thrombotic efficacy and low bleeding risks.