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

Cell Mol Life Sci. 2005 Jun;62(11):1198-220. doi: 10.1007/s00018-005-4533-5.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Disease
  • Drug Design*
  • Drug Therapy
  • Humans
  • Models, Molecular
  • Phosphodiesterase Inhibitors* / chemistry
  • Phosphodiesterase Inhibitors* / pharmacology
  • Phosphodiesterase Inhibitors* / therapeutic use
  • Phosphoric Diester Hydrolases* / chemistry
  • Phosphoric Diester Hydrolases* / drug effects
  • Protein Structure, Tertiary
  • Structure-Activity Relationship

Substances

  • Phosphodiesterase Inhibitors
  • Phosphoric Diester Hydrolases