**6. Clinical significance of YC-1**

Extensive studies have been conducted to explore possible systemic actions of YC-1 in disease models in animals to demonstrate that YC-1 has versatile physiological activities to be a potent candidate drug for a number of vascular disorders. In the cardiovascular and hematological systems, it has been reported that local extravascular administration of YC-1 could prevent neointima formation in a rat carotid artery model of balloon angioplasty [63, 64, 67]. In a study of experimental thrombosis model, YC-1 conferred beneficial effect through its anti-aggregating and pro-fibrinolytic effects [105]. BAY 63-2521 (riociguat™), a NO-independent but heme-dependent sGC stimulators like TC-1, is currently in clinical development for the treatment of pulmonary arterial hypertension with the only reported significant side effect to be a decrease in systemic arterial diastolic pressure [106, 107]. Similarly, intravenous administration of YC-1 has been shown to lower mean arterial blood pressure in normotensive and hypertensive rat [108]. For anticancer therapy, Lau et al. demonstrated that intraperitoneal injection of YC-1 enhances cisplatin chemosensitivity of hepatocellular carcinoma cells in nude mice xenograft tumor model, suggesting that YC-1 may be as an adjuvant agent for anticancer therapy [80]. Furthermore, oral administration of YC-1 can also decrease tumor mass in human renal cancer xenograft mice model [87]. In Morris water maze and avoidance test of mice, Chien et al. showed that YC-1 may be a good candidate for the improvement of learning and memory [94, 109]. Hwang et al. demonstrated that YC-1 can potentiate the relaxant responses of exogenous or endogenous NO through the elevation of cGMP in guinea-pig trachea [110]. The above in vivo studies all demonstrated the relevance of YC-1 in association with NO.
