Center for Cardiovascular Research, Charité-Universitätsmedizin Berlin, Hessische Str. 3-4, 10115 Berlin, Germany.
Curr Opin Pharmacol. 2011 Apr;11(2):187-92. doi: 10.1016/j.coph.2010.11.002. Epub 2010 Dec 15.
The renin-angiotensin-system harbours two main receptor subtypes binding angiotensin II which are the AT1-receptor and the AT2-receptor. While the AT1-receptor has been a drug target in cardiovascular disease for many years, the AT2-receptor was only a subject of academic interest. This has changed with the design and synthesis of a first non-peptide, orally active AT2-receptor agonist, compound 21 (C21). First data using C21 revealed tissue protective effects and functional improvement after myocardial infarction and in hypertension-induced end organ damage, notably in a blood-pressure independent way. In all of these models, AT2-receptor mediated anti-inflammation seemed an important underlying mechanism. C21 is awaited to enter a phase I clinical study in 2011.
肾素-血管紧张素系统包含两个主要的受体亚型，能与血管紧张素 II 结合，分别是 AT1 受体和 AT2 受体。虽然 AT1 受体多年来一直是心血管疾病的药物靶点，但 AT2 受体仅作为学术研究的课题。这一情况因首个非肽类、口服活性 AT2 受体激动剂化合物 21（C21）的设计和合成而改变。使用 C21 的首批数据显示，在心肌梗死和高血压引起的靶器官损伤中，C21 具有组织保护作用和功能改善作用，尤其是在血压独立的方式下。在所有这些模型中，AT2 受体介导的抗炎作用似乎是一个重要的潜在机制。C21 有望在 2011 年进入 I 期临床研究。
