Lificiguat (YC-1) is an nitric oxide (NO)-independent activator of soluble guanylyl cyclase(sGC) and an inhibitor of Hypoxia-inducible factor-1alpha (HIF-1alpha).

sGC (presence of CO):0.6-1.1 μM (Kd)

Lificiguat提高了可溶性鸟苷酸环化酶(sGC)的催化速率，并使该酶对其气体激活剂一氧化氮或一氧化碳更为敏感。单独使用Lificiguat时，酶的活性仅增加10倍，但它能增强CO和NO依赖的sGC激活，导致对高度纯化酶的刺激作用可能增加数百至数千倍。Lificiguat还能抑制血小板聚集和血管收缩，并在体外抑制HIF-1活性。在缺氧条件下培养的肝癌细胞中，Lificiguat完全阻断HIF-1α在转录后水平的表达，并因此抑制HIF-1的转录因子活性，这表明Lificiguat的这些效应很可能与氧感应途径相关，而非与可溶性鸟苷酸环化酶的激活有关。

在实验动物中，Lificiguat抑制富含血小板的血栓形成，并降低平均动脉压。Lificiguat有效抑制肿瘤携带小鼠中的肿瘤生长。在小鼠中，Lificiguat抑制肿瘤中HIF-1的活性，这与阻断血管生成以及抑制肿瘤生长相关联，而Lificiguat的抗血小板聚集效应似乎不影响肿瘤生长。

Hep3B cells are plated in a six-well plate at a density of 1 × 105 cells/well in α-modified Eagle medium supplemented with 10% heat-inactivated FBS and incubated overnight. Cells are treated with YC-1 (0.01-10 μM) or vehicle (DMSO) for 5 minutes and are then subjected to normoxia or hypoxia for 24 hours. VEGF levels in the conditioned media are quantified by using the Quantikine human VEGF Immunoassay kit. The VEGF concentrations are quantified by comparison with a series of VEGF standard samples included in the assay kit.

Animal Models: Male nude (BALB/cAnNCrj–nu/nu) mice. Formulation: DMSO. Dosages: 30 μg/g. Administration: i.p.