The Chemistry and Biology of Soluble Guanylate Cyclase Stimulators and Activators
The Chemistry and Biology of Soluble Guanylate Cyclase Stimulators and Activators
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DOI：
10.1002/anie.201302588
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发表时间：
2013-09-02
影响因子：
16.6
通讯作者：
Straub, Alexander
中科院分区：
文献类型：
--
作者：
Follmann, Markus;Griebenow, Nils;Straub, Alexander
一氧化氮(NO)的血管扩张特性已被用于药物治疗130多年。尽管如此，非捐赠者药物在心血管疾病的管理中仍然很重要。然而，吸入NO或释放NO的药物和有机硝酸盐与值得注意的治疗缺陷有关，包括某些疾病状态下对NO的抗药性，长期治疗过程中耐受性的形成，以及非特异性影响，如蛋白质的翻译后修饰。NO的有益作用是通过刺激可溶性鸟苷环化酶(SGC)介导的，sGC是一种含血红素的酶，产生细胞内信号分子环鸟苷一磷酸(CGMP)。最近发现了两类以非独立方式放大sGC功能的化合物，即所谓的sGC刺激剂和sGC激活剂。最先进的药物sGC刺激剂riociguat已经成功地对不同形式的肺动脉高压进行了III期临床试验。
The vasodilatory properties of nitric oxide (NO) have been utilized in pharmacotherapy for more than 130years. Still today, NO-donor drugs are important in the management of cardiovascular diseases. However, inhaled NO or drugs releasing NO and organic nitrates are associated with noteworthy therapeutic shortcomings, including resistance to NO in some disease states, the development of tolerance during long-term treatment, and nonspecific effects, such as post-translational modification of proteins. The beneficial actions of NO are mediated by stimulation of soluble guanylate cyclase (sGC), a heme-containing enzyme which produces the intracellular signaling molecule cyclic guanosine monophosphate (cGMP). Recently, two classes of compounds have been discovered that amplify the function of sGC in a NO-independent manner, the so-called sGC stimulators and sGC activators. The most advanced drug, the sGC stimulator riociguat, has successfully undergone PhaseIII clinical trials for different forms of pulmonary hypertension.