page_title: Discovery and development of phosphodiesterase 5 inhibitors
section_title: PDE5 Inhibitors
hierarchical_section_title: Discovery and development of phosphodiesterase 5 inhibitors / Development / The phosphodiesterase 5 enzyme / PDE5 Inhibitors
caption_attribution_description: English: Figure 3. PDE5 Domains
context_page_description: Phosphodiesterases are a superfamily of enzymes. This superfamily is further classified into 11 families, PDE1 - PDE11, on the basis of regulatory properties, amino acid sequences, substrate specificities, pharmacological properties and tissue distribution. Their function is to degrade intracellular second messengers such as cyclic adenine monophosphate and cyclic guanosine monophosphate which leads to several biological processes like effect on intracellular calcium level by the Ca²⁺ pathway.
  Phosphodiesterase 5 is widely expressed in several tissues in the body for example brain, lung, kidney, urinary bladder, smooth muscle and platelets. It is possible to prevent cGMP hydrolysis by inhibiting PDE5 and therefore treat diseases associated with low cGMP levels, because of this, PDE5 is an ideal target for the development of inhibitors. The therapeutic effects of PDE5 inhibition have been demonstrated in several cardiovascular conditions, chronic kidney disease and diabetes mellitus.
context_section_description: The PDE5 inhibitors sildenafil, vardenafil and tadalafil are competitive and reversible inhibitors of cGMP hydrolysis by the catalytic side of PDE5. The structures of vardenafil and sildenafil are similar, they both contain similar structured purine ring of cGMP that contributes their features to act as a competitive inhibitor of PDE5. The difference of the molecular structures is the reason for interaction with the catalytic site of PDE5 and improves the affinity of these compounds compared with cGMP selectivity.
caption: This caption uses trivial wording.  (July 2017)Figure 3. PDE5 Domains
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