Ataciguat, formerly named as HMR 1766, is a novel activator of soluble guanylyl cyclase (sGC) [1].

The sGC is activated in the presence of NO, converts GTP to cyclic GMP (cGMP). The sGC shows a direct role in controlling various physiological processes, including the cardiovascular and neural systems [2].

In aortic rings from CHF rats, ataciguat normalized the impaired endothelium-dependent, NO-mediated vasorelaxation as well as vascular sensitivity to exogenous NO. In platelets from CHF rats, ataciguat normalized the attenuated the in vivo VASP phosphorylation. Treatment with ataciguat reduced the platelet activation in CHF [1]. Ataciguat normalized platelet activation by reducing P-selectin expression and increasing platelet vasodilator stimulated phosphoprotein (VASP) phosphorylation. In isolated aortic rings from control and placebo treated STZ rats, activation of sGC by ataciguat normalized vascular function and restored endothelium dependent relaxation [3]. In a mouse model of coronary thrombosis, treatment with ataciguat significantly reduced atherosclerotic plaque formation and markedly improved endothelium-dependent vasodilatation. Ataciguat treatment showed no effect on endothelium-independent vasorelaxation or vasoconstriction. Ataciguat increased expression of vascular P-VASP, showed no effect on eNOS and sGC expression, and reduced vascular VCAM-1 expression [3].

References:
[1] Schfer A, Fraccarollo D, Werner L, et al.  Guanylyl cyclase activator ataciguat improves vascular function and reduces platelet activation in heart failure[J]. Pharmacological research, 2010, 62(5): 432-438.
[2] Poulos T L.  Soluble guanylate cyclase[J]. Current opinion in structural biology, 2006, 16(6): 736-743.
[3] van Eickels M, Wassmann S, Schfer A, et al.  Role of the sGC activator ataciguat sodium (HMR1766) in cardiovascular disease[J]. BMC Pharmacology, 2007, 7: 1-2.