Cyclic 3',5'-nucleotide phosphodiesterase (PDE) (PDE)

Cyclic 3',5'-nucleotide phosphodiesterases (PDEs) are a superfamily of enzymes that catalyze the hydrolysis of the second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) into their inactive 5'-monophosphate forms (Francis et al., 2011; Bender & Beavo, 2006). By regulating the intracellular concentrations of these messengers, PDEs play a pivotal role in modulating signal transduction pathways across various tissues, including the cardiovascular, respiratory, and nervous systems (Keravis & Lugnier, 2012). The PDE superfamily consists of 11 families (PDE1–PDE11), which differ in their substrate specificity, kinetic properties, and tissue distribution (StatPearls, 2024). Because of their central role in physiological regulation, PDEs are significant therapeutic targets for a wide range of conditions (Francis et al., 2011). For example, PDE5 inhibitors are widely used to treat erectile dysfunction and pulmonary arterial hypertension, while PDE4 inhibitors are utilized for inflammatory diseases like chronic obstructive pulmonary disease (COPD) and psoriasis (StatPearls, 2024; UniProt). PDE3 inhibitors are employed in the management of acute heart failure and intermittent claudication due to their effects on cardiac contractility and vasodilation (Bender & Beavo, 2006). The development of isoform-selective inhibitors remains a key strategy to maximize therapeutic efficacy while minimizing off-target side effects associated with non-selective inhibition (Keravis & Lugnier, 2012).

Other names

Phosphodiesterase3',5'-cyclic nucleotide phosphodiesteraseCyclic nucleotide phosphodiesterasePDE

Inhibition of the hydrolysis of cAMP and/or cGMP, leading to increased intracellular levels of these second messengers and prolonged activation of their respective signaling pathways (StatPearls, 2024; Francis et al., 2011).