3',5'-cyclic-AMP phosphodiesterase (cAMP-PDE) (cAMP-PDE)

3',5'-cyclic-AMP phosphodiesterases (cAMP-PDEs) are a class of enzymes responsible for the degradation of the second messenger cyclic adenosine monophosphate (cAMP) into 5'-adenosine monophosphate (5'-AMP) [1, 2]. By controlling the duration and amplitude of cAMP signaling, these enzymes regulate a wide array of cellular functions, including inflammation, cardiac contractility, and smooth muscle tone [2, 3]. The cAMP-PDE family is diverse, comprising cAMP-specific isoforms like PDE4, PDE7, and PDE8, as well as dual-specificity enzymes such as PDE1, PDE2, and PDE3 [1, 4]. Dysregulation of cAMP-PDE activity is implicated in several chronic conditions, particularly inflammatory diseases like asthma, COPD, and psoriasis, where excessive PDE activity reduces cAMP levels and promotes pro-inflammatory states [3, 5]. Therapeutic targeting of these enzymes, primarily through PDE4 inhibition, aims to elevate intracellular cAMP to suppress cytokine production and induce bronchodilation [5, 6]. Clinically approved drugs such as roflumilast and apremilast demonstrate the efficacy of targeting cAMP-PDEs in managing respiratory and dermatological disorders [6]. However, the broad expression of these enzymes across different tissues can lead to side effects like gastrointestinal distress and psychiatric symptoms, presenting a challenge for drug development [4, 5].

Other names

Cyclic AMP phosphodiesterasecAMP phosphodiesteraseCyclo-AMP phosphodiesterase3',5'-cyclic-nucleotide phosphodiesterase (cAMP-specific)cAMP-specific phosphodiesterase

Inhibition of the hydrolysis of cAMP to 5'-AMP, leading to increased intracellular cAMP levels and subsequent activation of cAMP-dependent pathways such as PKA and EPAC signaling.