Cyclic nucleotide phosphodiesterase (PDE) (PDE)

Cyclic nucleotide phosphodiesterases (PDEs) are a superfamily of enzymes that catalyze the breakdown of the second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) into their inactive 5'-monophosphate forms [StatPearls: NBK559276]. By controlling the duration and amplitude of cyclic nucleotide signaling, PDEs regulate a vast array of physiological processes, including cardiac contractility, vascular tone, and inflammatory responses [PubMed: 25183370]. The PDE superfamily consists of 11 families (PDE1–PDE11), which differ in their substrate specificity, tissue distribution, and regulatory mechanisms [UniProt: P54750]. Dysregulation of PDE activity is implicated in numerous pathologies, such as cardiovascular disease, respiratory disorders, and erectile dysfunction [Wikipedia: Phosphodiesterase]. Consequently, PDEs are major therapeutic targets; for instance, PDE5 inhibitors are used for erectile dysfunction and pulmonary hypertension, while PDE4 inhibitors are employed in treating chronic inflammatory conditions like psoriasis and COPD [StatPearls: NBK559276]. The development of isoform-selective inhibitors is a primary focus in drug discovery to minimize side effects associated with non-selective inhibition across different tissues [PubMed: 30103318]. These enzymes are characterized by a conserved catalytic domain but vary significantly in their N-terminal regulatory regions, allowing for precise spatial and temporal control of signaling [PubMed: 25183370].

Other names

PhosphodiesterasePDE family3',5'-cyclic-nucleotide phosphodiesteraseCyclic nucleotide hydrolase

Inhibition of the hydrolysis of cyclic adenosine monophosphate (cAMP) and/or cyclic guanosine monophosphate (cGMP), thereby increasing intracellular concentrations of these second messengers and prolonging their downstream signaling effects.