Cellular and Molecular Life Sciences CMLS

, Volume 62, Issue 11, pp 1198-1220

First online:

Phosphodiesterase: overview of protein structures, potential therapeutic applications and recent progress in drug development

  • Y. H. JeonAffiliated withR&D Center, CrystalGenomics
  • , Y. -S. HeoAffiliated withR&D Center, CrystalGenomics
  • , C. M. KimAffiliated withR&D Center, CrystalGenomics
  • , Y. -L. HyunAffiliated withR&D Center, CrystalGenomics
  • , T. G. LeeAffiliated withR&D Center, CrystalGenomics
  • , S. RoAffiliated withR&D Center, CrystalGenomics
  • , J. M. ChoAffiliated withR&D Center, CrystalGenomics Email author 

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Phosphodiesterases (PDEs) are essential regulators of cyclic nucleotide signaling with diverse physiological functions. Because of their great market potential and therapeutic importance, PDE inhibitors became recognized as important therapeutic agents in the treatment of various diseases. Currently, there are seven PDE inhibitors on the market, and the pharmacological and safety evaluations of many drug candidates are in progress. Three-dimensional (3D) structures of catalytic domains of PDE 1, -3, -4, -5 and -9 in the presence of their inhibitors are now available, and can be utilized for rational drug design. Recent advances in molecular pharmacology of PDE isoenzymes resulted in identification of new potential applications of PDE inhibitors in various therapeutic areas, including dementia, depression and schizophrenia. This review will describe the latest advances in PDE research on 3D structural studies, the potential of therapeutic applications and the development of drug candidates.

Key words.

Phosphodiesterase cAMP cGMP 3D structure drug discovery