Background: Phosphodiesterases (PDEs) are a critical class of enzymes that regulate cellular levels of cyclic nucleotides, such as cAMP and cGMP, by catalyzing their hydrolysis. Dysregulation of PDE activity is associated with a wide range of diseases, including erectile dysfunction, pulmonary hypertension, and neurodegenerative disorders. By targeting specific PDE isoforms with inhibitors, researchers can modulate cyclic nucleotide levels, thereby influencing cellular responses and physiological processes. This makes PDEs an important target in therapeutic development.

Detection of PDE Activity: We detect PDE hydrolytic activity by monitoring the hydrolysis of phosphodiester bonds in dye-labeled cyclic nucleotides. Following the hydrolysis by PDEs, the resulting nucleotide monophosphate is exposed, allowing for the addition of beads with a high affinity for the monophosphate. This binding interaction alters the motion rate of the fluorescent molecule complex, generating high fluorescence polarization (FP) signal values. The degree of cyclic nucleotide hydrolysis by PDEs, as measured by FP, directly reflects the effectiveness of small molecule inhibitors targeting these enzymes.

Quality Control and System Validation: In our PDE assays, we utilize FDA-approved drugs or inhibitors under development as quality control molecules to ensure the stability and sensitivity of our system. This rigorous validation process allows us to produce results that are highly consistent with published data, providing our clients with reliable and reproducible insights into PDE inhibition.

Comprehensive PDE Evaluation Services: We offer a wide range of evaluation services for PDE selective inhibitors, covering tests for 11 different PDE subtypes and 25 common targets, including several key isoforms within the same subtype. Our services are designed to assess the selectivity of inhibitors across different PDE subtypes, as well as within specific subtypes, such as the 10 targets within the PDE4 subtype. This comprehensive approach allows us to deliver detailed assessments of potential therapeutic compounds, supporting the development of highly targeted PDE inhibitors.