Nelociguat

Nelociguat (BAY60-4552) is a nitric oxide sensitive soluble guanylate cyclase stimulator. In Vitro: Soluble guanylate cyclase (sGC) is a key enzyme in the nitric oxide (NO) signalling pathway^[1]. Riociguat is metabolized to BAY60-4552 not only via cytochrome P450 isoenzymes 3A4 (CYP3A4), CYP2C8, and CYP2J2, but also via CYP1A1, located in the liver and lungs^[2]. In Vivo: GSK2181236A and BAY 60-4552 provide partial benefit against hypertension-induced end-organ damage. In spontaneously hypertensive stroke-prone rats, a low dose of BAY 60-4552 decreases urine output and improved survival. A high dose also reduces urine output, and in addition reduces microalbuminuria and attenuates the increase in mean arterial pressure. Both the 0.3 and 3 mg/kg/day doses of BAY 60-4552 improves survival of 46 and 69%. Seven weeks of treatment with BAY 60-4552 (0.3 and 3.0 mg/kg/day) dose-dependently decreases urine output to 79±11 and 56±10 mL/day^[1]. BAY 60-4552, and vardenafil provides synergistic beneficial effects and might therefore salvage patients who experience treatment failures with PDE5 inhibitors after radical prostatectomy^[3].