Evgenov Oleg V, Pacher Pál, Schmidt Peter M, Haskó György, Schmidt Harald H H W, Stasch Johannes-Peter
Department of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, CLN 309, Boston, Massachusetts 02114, USA.
Nat Rev Drug Discov. 2006 Sep;5(9):755-68. doi: 10.1038/nrd2038.
Soluble guanylate cyclase (sGC) is a key signal-transduction enzyme activated by nitric oxide (NO). Impaired bioavailability and/or responsiveness to endogenous NO has been implicated in the pathogenesis of cardiovascular and other diseases. Current therapies that involve the use of organic nitrates and other NO donors have limitations, including non-specific interactions of NO with various biomolecules, lack of response and the development of tolerance following prolonged administration. Compounds that activate sGC in an NO-independent manner might therefore provide considerable therapeutic advantages. Here we review the discovery, biochemistry, pharmacology and clinical potential of haem-dependent sGC stimulators (including YC-1, BAY 41-2272, BAY 41-8543, CFM-1571 and A-350619) and haem-independent sGC activators (including BAY 58-2667 and HMR-1766).
可溶性鸟苷酸环化酶（sGC）是一种由一氧化氮（NO）激活的关键信号转导酶。内源性NO的生物利用度受损和/或反应性受损与心血管疾病和其他疾病的发病机制有关。目前涉及使用有机硝酸盐和其他NO供体的治疗方法存在局限性，包括NO与各种生物分子的非特异性相互作用、缺乏反应以及长期给药后耐受性的发展。因此，以不依赖NO的方式激活sGC的化合物可能具有相当大的治疗优势。在这里，我们综述了血红素依赖性sGC刺激剂（包括YC-1、BAY 41-2272、BAY 41-8543、CFM-1571和A-350619）和血红素非依赖性sGC激活剂（包括BAY 58-2667和HMR-1766）的发现、生物化学、药理学及临床潜力。
