Regado Biosciences, Inc., 318 Blackwell St, STE 130, Durham, NC 27701, USA.
Arterioscler Thromb Vasc Biol. 2010 Mar;30(3):382-7. doi: 10.1161/ATVBAHA.110.203117. Epub 2010 Feb 5.
Venous thromboembolism remains a frequent cause of vascular death. Despite advances in anticoagulant drug development, unmet needs remain, including limited treatment options for patients with severe renal impairment and the inability to fully reverse the effects of anticoagulants approved or in late-stage development. Because coagulation factor IXa plays a pivotal role in tissue factor-mediated thrombin generation, it represents an attractive target for anticoagulant development. This article discusses the rationale for factor IXa as an anticoagulant target and the potential role in venous thromboembolism prevention or management of the 2 factor IXa inhibitors that have undergone testing in phase 1 or 2 trials: TTP889, an oral, small-molecule compound, and RB006, an aptamer-based compound, the intravenous and subcutaneous formulations of which are the anticoagulant components of the REG1 and REG2 anticoagulation systems, respectively.
静脉血栓栓塞仍然是血管死亡的常见原因。尽管抗凝药物的开发取得了进展，但仍存在未满足的需求，包括严重肾功能损害患者的治疗选择有限，以及无法完全逆转已批准或处于后期开发阶段的抗凝剂的作用。由于凝血因子 IXa 在组织因子介导的凝血酶生成中起关键作用，因此它是抗凝开发的一个有吸引力的靶点。本文讨论了因子 IXa 作为抗凝靶点的原理，以及在静脉血栓栓塞预防或管理中，在 1 期或 2 期临床试验中进行测试的 2 种因子 IXa 抑制剂的潜在作用：TTP889，一种口服小分子化合物，和 RB006，一种基于适配体的化合物，其静脉内和皮下制剂分别是 REG1 和 REG2 抗凝系统的抗凝成分。
