Small-molecule inhibitors of protein-protein interactions

Curr Opin Drug Discov Devel. 2008 Sep;11(5):666-74.

Abstract

Protein-protein interactions regulate almost all aspects of cellular signaling and aberrant protein-protein interactions have the potential to cause or contribute to human disease. The modulation of these interactions by drug-like molecules would offer previously unavailable opportunities to explore the relevance of pre-selected protein-protein interactions for cellular signaling, as well as benefits to patients. After an initial period of skepticism with regards to feasibility, there is now an encouraging set of data indicating that the effective and selective modulation of protein-protein interactions by drug-like molecules is attainable. This review highlights selected areas of current research that are aimed at identifying potent inhibitors of disease-relevant protein-protein interactions.

Publication types

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

MeSH terms

  • ADP-Ribosylation Factor 1 / antagonists & inhibitors
  • Animals
  • Apoptosis / drug effects
  • Binding Sites
  • Caspase Inhibitors
  • Cell Cycle Proteins / antagonists & inhibitors
  • Core Binding Factor Alpha 2 Subunit / antagonists & inhibitors
  • Drug Design*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • GTPase-Activating Proteins / antagonists & inhibitors
  • Humans
  • Molecular Structure
  • Nitric Oxide Synthase Type II / antagonists & inhibitors
  • Oncogene Proteins, Fusion / antagonists & inhibitors
  • PDZ Domains
  • Protein Binding
  • Protein Interaction Mapping*
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Proteins / antagonists & inhibitors*
  • Proteins / chemistry
  • Proteins / metabolism
  • Proto-Oncogene Proteins / antagonists & inhibitors
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
  • Proto-Oncogene Proteins c-mdm2 / antagonists & inhibitors
  • Signal Transduction / drug effects
  • Tumor Suppressor Protein p53 / antagonists & inhibitors
  • X-Linked Inhibitor of Apoptosis Protein / antagonists & inhibitors

Substances

  • CBFbeta-MYH11 fusion protein
  • Caspase Inhibitors
  • Cell Cycle Proteins
  • Core Binding Factor Alpha 2 Subunit
  • Enzyme Inhibitors
  • GTPase-Activating Proteins
  • Oncogene Proteins, Fusion
  • Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • X-Linked Inhibitor of Apoptosis Protein
  • cytohesin-2
  • Nitric Oxide Synthase Type II
  • Proto-Oncogene Proteins c-mdm2
  • Protein-Serine-Threonine Kinases
  • polo-like kinase 1
  • ADP-Ribosylation Factor 1