Inhibitor Phosphodiesterase

cAMP and cGMP, two important second messengers molecules are hydrolyzed by phosphodiesterases (PDEs) in the cell, leading to cessation of cAMP and cGMP-dependent effects. PDEs comprise a large group of enzymes organized into 11 distinct families based on their biochemical and molecular properties. Many of these isozymes are differently expressed and regulated in different cells and exhibit distinct selectivity for cAMP and cGMP. PDEs contain three functional domains: a regulatory N-terminus, a central catalytic domain, and a regulatory C- terminus. All isozymes exhibit significant homology in their catalytic domain. The N- and C-terminal domains also display moderate homology within families and impart specific characteristics to different subtypes. The N-terminus is involved in allosteric regulation and membrane targeting. The C-terminus is believed to be involved in dimerization and possess docking sites for PDEspecific kinases.

Due to their involvement in inflammation, asthma, and cardiovascular complications, erectile dysfunctions, PDEs are considered to be attractive targets for pharmacological intervention. Erectile dysfunction is a common multi-factorial complication of diabetes mellitus and PDE V inhibitor therapy has been found to be effective in special clinical populations, such as those with prostate cancer, diabetes, and cardiovascular disease.

Classification of Phosphodiesterases