Mechanism investigation of highly selective inhibitors toward phosphodiesterase 5 and 6 via the in vitro calculation and simulation

In clinical practice, phosphodiesterase 5 (PDE5) inhibitors are commonly used to treat erectile dysfunction and pulmonary arterial hypertension. However, due to the high structural similarity between PDE5 and Phosphodiesterase 6 (PDE6), there is a risk that existing drugs will cause off-target effects on PDE6 resulting in visual disorders such as low visual acuity and color blindness. Previous research on the selectivity of PDE5 inhibitors focused on marketed drugs such as sildenafil and tadalafil.