Nelociguat (BAY60-4552) (Synonyms: BAY 60-4552, Desmethyl Riociguat)

Nelociguat (BAY60-4552) is a nitric oxide sensitive soluble guanylate cyclase stimulator.

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].

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].

[1]. Costell MH, et al. Comparison of soluble guanylate cyclase stimulators and activators in models of cardiovascular disease associated with oxidative stress. Front Pharmacol. 2012 Jul 5;3:128. [2]. Zhao X, et al. Pharmacokinetics of the Soluble Guanylate Cyclase Stimulator Riociguat in Healthy Young Chinese Male Non-Smokers and Smokers: Results of a Randomized, Double-Blind, Placebo-Controlled Study. Clin Pharmacokinet. 2016 May;55(5):615-24. [3]. Oudot A, et al. Combination of BAY 60-4552 and vardenafil exerts proerectile facilitator effects in rats with cavernous nerve injury: a proof of concept study for the treatment of phosphodiesterase type 5 inhibitor failure. Eur Urol. 2011 Nov;60(5):1020-6.