Small-molecule stabilization of protein-protein interactions: an underestimated concept in drug discovery?

Angew Chem Int Ed Engl. 2012 Feb 27;51(9):2012-8. doi: 10.1002/anie.201107616. Epub 2012 Feb 3.

Abstract

The modulation of protein-protein interactions (PPIs) has been recognized as one of the most challenging tasks in drug discovery. While their systematic development has long been considered as intractable, this view has changed over the last years, with the first drug candidates undergoing clinical studies. To date, the vast majority of PPI modulators are interaction inhibitors. However, in many biological contexts a prolonged lifespan of a PPI might be desirable, calling for the complementary approach of PPI stabilization. In fact, nature offers impressive examples of this concept and some PPI-stabilizing natural products have already found application as important drugs. Moreover, directed small-molecule stabilization has recently been demonstrated. Therefore, it is time to take a closer look at the constructive side of modulating PPIs.

Publication types

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

MeSH terms

  • Animals
  • Biological Products / chemistry
  • Biological Products / pharmacology*
  • Drug Discovery* / methods
  • Humans
  • Models, Molecular
  • Protein Binding / drug effects*
  • Protein Interaction Mapping*
  • Proteins / chemistry
  • Proteins / metabolism*
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*

Substances

  • Biological Products
  • Proteins
  • Small Molecule Libraries