Modulators of protein-protein interactions: novel approaches in targeting protein kinases and other pharmaceutically relevant biomolecules

Curr Top Med Chem. 2011;11(11):1305-19. doi: 10.2174/156802611795589610.

Abstract

In recent years the development of small organic molecules modulating protein-protein interactions (P-PIs) has drawn major attention in both academic and industrial research. Despite the appreciable progress being made, targeting such extensive interaction areas with comparatively small, drug-like agents has proven to be an ambitious objective. This review highlights the reasons rendering this task highly challenging and provides an overview on the latest developments in rational design approaches for P-PI modulators. The significance, scope and limitations of computational methods in this particular field of research are analyzed. Recent successfully identified and designed P-PI modulators are discussed. Thereby, particular focus is taken on small organic molecules disrupting protein-protein interfaces of protein kinases.

Publication types

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

MeSH terms

  • Computational Biology
  • Drug Design*
  • Humans
  • Molecular Dynamics Simulation
  • Molecular Targeted Therapy
  • Organic Chemicals / chemical synthesis
  • Organic Chemicals / chemistry
  • Organic Chemicals / pharmacology*
  • Protein Binding / drug effects
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinases / metabolism*

Substances

  • Organic Chemicals
  • Protein Kinase Inhibitors
  • Protein Kinases