Unraveling phosphodiesterase surfaces. Identification of phosphodiesterase 7 allosteric modulation cavities

Eur J Med Chem. 2013:70:781-8. doi: 10.1016/j.ejmech.2013.10.035. Epub 2013 Oct 22.

Abstract

The last findings of our group by using chemical genetic approaches have shown that PDE7 is an interesting target in neurodegenerative diseases. The following step in this travel to unravel PDE7 is the design of more selective inhibitors. In this sense we have proposed to perform an analysis of PDE7 surface to identify possible allosteric sites following by a docking study of different PDE7 inhibitors synthesized by our group. Thanks to these studies we have proved the existence of allosteric sites in PDE7 and we have been able to explain the binding modes of the employed PDE7 inhibitors.

Keywords: Allosteric sites; Docking; Neurodegeneration; PDE7; Surface study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allosteric Regulation / drug effects
  • Allosteric Site / drug effects
  • Cyclic Nucleotide Phosphodiesterases, Type 7 / antagonists & inhibitors*
  • Cyclic Nucleotide Phosphodiesterases, Type 7 / metabolism
  • Dose-Response Relationship, Drug
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Phosphodiesterase Inhibitors / chemistry
  • Phosphodiesterase Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • Surface Properties

Substances

  • Phosphodiesterase Inhibitors
  • Cyclic Nucleotide Phosphodiesterases, Type 7
  • PDE7A protein, human