cGMP-specific 3',5'-cyclic phosphodiesterase type 5 (PDE5)

cGMP-specific 3',5'-cyclic phosphodiesterase type 5 (PDE5) is a key enzyme responsible for the degradation of cyclic guanosine monophosphate (cGMP) into 5'-GMP, primarily in vascular smooth muscle cells [1, 15]. By regulating cGMP levels, PDE5 plays a critical role in the nitric oxide (NO)/cGMP signaling pathway, which mediates smooth muscle relaxation and vasodilation [4, 8]. It is highly expressed in the corpus cavernosum, pulmonary vasculature, and platelets, making it a major therapeutic target for conditions characterized by impaired blood flow [6, 7]. PDE5 inhibitors, such as sildenafil and tadalafil, are widely used to treat erectile dysfunction and pulmonary arterial hypertension by prolonging the effects of cGMP [3, 14]. Beyond these indications, PDE5 is being investigated for its roles in heart failure, benign prostatic hyperplasia, and neurodegenerative diseases [9, 12]. However, its use is associated with safety concerns like severe hypotension when combined with nitrates, as well as potential off-target effects on other phosphodiesterase isoforms [11, 14].

Other names

PDE5ACGB-PDECN5APhosphodiesterase 5AcGMP-binding cGMP-specific phosphodiesterase

PDE5 inhibitors bind to the catalytic site of the enzyme, preventing the hydrolysis of cGMP to 5'-GMP. This leads to an accumulation of intracellular cGMP, which activates cGMP-dependent protein kinase (PKG), ultimately resulting in smooth muscle relaxation and vasodilation [4, 8, 15].