Phosphodiesterase type 1 (PDE1)

Phosphodiesterase type 1 (PDE1) is an enzyme family that regulates the intracellular levels of the second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). PDE1 is unique among phosphodiesterases as it is activated by calcium/calmodulin (Ca2+/CaM), making its activity dependent on intracellular calcium levels. The PDE1 family includes three main genes/isoforms: PDE1A, PDE1B, and PDE1C. Isoform differences affect substrate specificity. By regulating cAMP/cGMP signaling pathways, PDE1 enzymes play roles in memory formation, cardiac function, smooth muscle activity and more. Dysregulation is implicated in neurodegenerative diseases, cardiovascular disorders, metabolic syndromes, certain cancers, renal pathologies, and pulmonary hypertension. Selective inhibition or modulation of specific PDE１ isoforms is being explored for therapeutic intervention but challenges remain regarding selectivity due to high homology between isoforms/subtypes within the family.

Phosphodiesterase 1 Inhibitors