Cyclic GMP-Hydrolyzing Phosphodiesterases

cGMP-Dependent Protein Kinases and cGMP Phosphodiesterases in Nitric Oxide and cGMP Action

“…It also increases the V max of the enzyme and affinity of the allosteric sites for cGMP (Wyatt et al, 1998;Corbin et al, 2000;Rybalkin et al, 2002). Both cGMP binding to allosteric sites in PDE5 and its phosphorylation by PKGI contribute importantly to a powerful negative feedback on NO/cGMP/ PKGI signaling (see section IV.D.4) Rybalkin et al, 2002;Mullershausen et al, 2003;Francis et al, 2009). …”

“…The potential impact of such compounds has already been demonstrated with the therapeutic and marketing success of three PDE5-selective inhibitors, sildenafil, vardenafil, and tadalafil, which bind to the PDE5 catalytic site, thereby blocking access and hydrolysis of cGMP (Jeremy et al, 1997;Corbin, 2003, 2005;Carson, 2005;Porst et al, 2006;Francis et al, 2009). More of these PDE5 inhibitors are making their way into the commercial market (Kouvelas et al, 2009).…”

Mammalian Cyclic Nucleotide Phosphodiesterases: Molecular Mechanisms and Physiological Functions

“…PDE inhibitors that are in clinical use include PDE5 inhibitors for treatment of ED and pulmonary hypertension (23, 55,82,97,112,119,120,242,255,284,306,359), PDE3 inhibitors for treatment of intermittent claudication and acute cardiac failure (180,181,242,260), a PDE4 inhibitor for treatment of COPD (139), a nonspecific PDE inhibitor (theophylline) for treatment of asthma (22), and dipyridamole, a relatively nonspecific PDE inhibitor for prevention of blood clotting following stroke or heart valve replacement (51, 91). Many new PDE inhibitors are being developed to provide improved treatment of these and other maladies.…”

Mechanisms of Penile Erection and Basis for Pharmacological Treatment of Erectile Dysfunction

“…SLx-2101. The available information on SLx-2101 is scarce and most of it is published in abstract form (Hatzimouratidis and Hatzichristou, 2008;Palit and Eardley, 2010), but a structure is provided in Francis et al (2009). SLx-2101 is a selective, fast-onset PDE5 inhibitor that is converted to an active metabolite, SLx-2081 (Myatt and Eardley, 2008).…”