Riociguat: Mode of Action and Clinical Development in Pulmonary Hypertension
Riociguat: Mode of Action and Clinical Development in Pulmonary Hypertension
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DOI：
10.1016/j.chest.2016.05.024
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发表时间：
2017-02-01
期刊：
影响因子：
9.6
通讯作者：
Klinger, James R.
中科院分区：
文献类型：
--
作者：
Ghofrani, Hossein-Ardeschir;Humbert, Marc;Klinger, James R.
肺动脉高压（PAH）和慢性血栓栓塞性肺动脉高压（CTEPH）是进行性和衰弱性疾病，其特征是肺血管系统逐渐阻塞，导致肺动脉压力（PAP）升高和肺血管阻力（PVR）增加。如果不及时治疗，可能会因右心衰竭而导致死亡。 Riociguat 是一种新型可溶性鸟苷酸环化酶 (sGC) 刺激剂，被批准用于治疗 PAH 和 CTEPH。我们详细描述了一氧化氮-sGC-环磷酸鸟苷 (cGMP) 信号通路在 PAH 和 CTEPH 发病机制中的作用以及利奥西呱的作用模式。我们还回顾了与利奥西呱开发相关的临床前数据，以及来自 PAH 和 CTEPH 的初始临床试验和关键 III 期随机临床试验的利奥西呱的疗效和安全性数据。
Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are progressive and debilitating diseases characterized by gradual obstruction of the pulmonary vasculature, leading to elevated pulmonary artery pressure (PAP) and increased pulmonary vascular resistance (PVR). If untreated, they can result in death due to right-sided heart failure. Riociguat is a novel soluble guanylate cyclase (sGC) stimulator that is approved for the treatment of PAH and CTEPH. We describe in detail the role of the nitric oxide-sGC-cyclic guanosine monophosphate (cGMP) signaling pathway in the pathogenesis of PAH and CTEPH and the mode of action of riociguat. We also review the preclinical data associated with the development of riociguat, along with the efficacy and safety data of riociguat from initial clinical trials and pivotal phase III randomized clinical trials in PAH and CTEPH.