Discovery of potent PDE4 inhibitors

Advisor(s)

Dr. Timothy Hagen, Northern Illinois University

Location

Room A119-2

Start Date

26-4-2019 11:05 AM

End Date

26-4-2019 11:20 AM

Abstract

The phosphodiesterase 4 (PDE4) enzyme, which is responsible for hydrolyzing cAMP in immune cells and the central nervous system, is involved in conditions such as Alzheimer’s disease, schizophrenia, and depression, making it a promising target for pharmaceutical development. Drugs such as Apremilast and Crisaborole are already in use. Ligands which act as inhibitors of PDE4 and have high binding affinity to the active sites, thereby increasing levels of cAMP in immune cells, are being investigated to treat patients with these conditions. Through computerized molecular docking experiments, a common method used in drug design and discovery, we bound different small molecules from the protein data bank (PDB) to binding sites of the PDE4 enzyme. Using the results of the experiments conducted with AutoDockTools, we were able to determine preferred orientations or poses of the ligands as well as their binding affinity to PDE4. Further study needs to be done on PDE4 inhibitors in order to understand PDE4 regulation and treat conditions impacted by it.

Share

COinS
 
Apr 26th, 11:05 AM Apr 26th, 11:20 AM

Discovery of potent PDE4 inhibitors

Room A119-2

The phosphodiesterase 4 (PDE4) enzyme, which is responsible for hydrolyzing cAMP in immune cells and the central nervous system, is involved in conditions such as Alzheimer’s disease, schizophrenia, and depression, making it a promising target for pharmaceutical development. Drugs such as Apremilast and Crisaborole are already in use. Ligands which act as inhibitors of PDE4 and have high binding affinity to the active sites, thereby increasing levels of cAMP in immune cells, are being investigated to treat patients with these conditions. Through computerized molecular docking experiments, a common method used in drug design and discovery, we bound different small molecules from the protein data bank (PDB) to binding sites of the PDE4 enzyme. Using the results of the experiments conducted with AutoDockTools, we were able to determine preferred orientations or poses of the ligands as well as their binding affinity to PDE4. Further study needs to be done on PDE4 inhibitors in order to understand PDE4 regulation and treat conditions impacted by it.