Phosphodiesterase 3A, 3B, and 10A (PDE3A, PDE3B, PDE10A)

Phosphodiesterase 3A and 3B are members of the cGMP-inhibited phosphodiesterase family, acting as enzymes that hydrolyze cAMP and cGMP to regulate cellular signaling. PDE3A is primarily expressed in cardiovascular tissues and platelets, where it regulates cardiac contractility and vascular smooth muscle tone, while PDE3B is more prevalent in tissues involved in energy metabolism (adipose, liver) and contributes to metabolic regulation. PDE10A, not detailed in these search results, is known as a dual-substrate phosphodiesterase predominantly expressed in the brain and is a target for drugs aimed at psychiatric and neurodegenerative diseases (not cardiac). Several drugs, including milrinone and anagrelide, target PDE3A/B enzymatic activity to exert therapeutic or research effects, but their clinical application is limited by safety concerns, notably the risk of arrhythmia and increased mortality in heart failure. Newer agents, such as DNMDP, are being developed as precision cancer therapies by exploiting interactions between PDE3A and apoptotic cofactors such as SLFN12.

Other names

cGMP-inhibited phosphodiesterase AcGMP-inhibited cAMP phosphodiesterase AcGMP-inhibited phosphodiesterase B

Inhibition of PDE3A/B increases intracellular cAMP/cGMP, leading to enhanced cardiac contractility and vasodilation, but may cause arrhythmias. Some drugs act as "molecular glue" between PDE3A and SLFN12 to induce apoptosis in cancer cells.