Chemical and structural lessons from recent successes in protein-protein interaction inhibition (2P2I)

Curr Opin Chem Biol. 2011 Aug;15(4):475-81. doi: 10.1016/j.cbpa.2011.05.024. Epub 2011 Jun 22.


Worldwide research efforts have driven recent pharmaceutical successes, and consequently, the emerging role of Protein-Protein Interactions (PPIs) as drug targets has finally been widely embraced by the scientific community. Inhibitors of these Protein-Protein Interactions (2P2Is or i-PPIs) are likely to represent the next generation of highly innovative drugs that will reach the market over the next decade. This review describes up-to-date knowledge on this particular chemical space, with a specific emphasis on a subset of this ensemble. We also address current structural knowledge regarding both protein-protein and protein-inhibitor complexes, that is, the 2P2I database. Finally, ligand efficiency analyses permit us to relate potency to size and polarity and to discuss the need to co-develop nanoparticle drug delivery systems.

Publication types

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

MeSH terms

  • Computer Simulation
  • Drug Design*
  • Humans
  • Ligands
  • Models, Chemical*
  • Molecular Structure
  • Protein Binding / physiology
  • Protein Conformation
  • Protein Interaction Mapping / methods*
  • Protein Structure, Secondary
  • Proteins / antagonists & inhibitors*
  • Proteins / chemistry


  • Ligands
  • Proteins