Transplantation Center, Department of Medicine, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne (UNIL), Chemin des Boveresses 155, CH1011 Lausanne, Switzerland.
J Med Chem. 2020 Mar 12;63(5):1978-1995. doi: 10.1021/acs.jmedchem.9b01780. Epub 2020 Feb 20.
The active hormone of the renin-angiotensin system (RAS), angiotensin II (Ang II), is involved in several human diseases, driving the development and clinical use of several therapeutic drugs, mostly angiotensin I converting enzyme (ACE) inhibitors and angiotensin receptor type I (ATR) antagonists. However, angiotensin peptides can also bind to receptors different from ATR, in particular, angiotensin receptor type II (ATR), resulting in biological and physiological effects different, and sometimes antagonistic, of their binding to ATR. In the present Perspective, the components of the RAS and the therapeutic tools developed to control it will be reviewed. In particular, the characteristics of ATR and tools to modulate its functions will be discussed. Agonists or antagonists to ATR are potential therapeutics in cardiovascular diseases, for agonists, and in the control of pain, for antagonists, respectively. However, controlling their binding properties and their targeting to the target tissues must be optimized.
肾素-血管紧张素系统（RAS）的活性激素血管紧张素 II（Ang II）参与多种人类疾病，推动了几种治疗药物的发展和临床应用，这些药物大多为血管紧张素转化酶（ACE）抑制剂和血管紧张素受体 I（ATR）拮抗剂。然而，血管紧张素肽也可以与不同于 ATR 的受体结合，特别是血管紧张素受体 II（ATR），导致与其结合的生物学和生理学效应不同，有时甚至拮抗。在本述评中，我们将回顾 RAS 的组成部分和为控制其功能而开发的治疗工具。特别是，我们将讨论 ATR 的特性和调节其功能的工具。ATR 的激动剂或拮抗剂分别是心血管疾病的潜在治疗药物（激动剂）和疼痛控制药物（拮抗剂）。然而，必须优化其结合特性及其对靶组织的靶向性。
