The soluble guanylate cyclase (s GC) is a key signal transduction enzyme in the nitric oxide (NO) -sGC-cyclic guanosine monophosphate (cGMP) pathway, which can be activated by NO and thus catalyzes the conversion of guanosine triphosphate (GTP) into the c GMP. As a second messenger, cGMP modulates the activity of downstream effectors, including the cGMP-dependent protein kinases (cGK), cGMP-dependent phosphodiesterases (PDE) and ion-gated channels, and ultimately participates in the regulation of several physiological functions, including the function of cardiovascular, gastrointestinal and central nervous systems. sGC stimulators could not only directly stimulate s GC but also synergistically act with NO to increase the sGC enzyme activity, which has shown a great potential to treat various diseases via regulating the NO-s GC-cGMP signaling pathway. Here, we give an overview of NOindependent sGC stimulators in clinical trial.%可溶性鸟苷酸环化酶(sGC)是一氧化氮(NO)-s GC-环鸟苷酸(c GMP)信号通路的关键传导酶.NO通过与sGC结合形成复合物,从而激活s GC;被激活的sGC通过C端催化域的作用催化GTP转化为cGMP;c GMP作为第二信使调节下游多种效应分子,如c GMP依赖蛋白激酶G、cGMP依赖磷酸二酯酶及cGMP门控离子通道,参与心血管系统、消化系统、中枢神经系统生理调节.sGC刺激剂可直接激活s GC,也可与NO协同作用,增加sGC酶活性,通过调节NO-sGC-c GMP信号通路治疗多种疾病.本文对处于临床研究的非NO依赖sGC刺激剂的研究进展进行综述.
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