1932

Abstract

Protein-protein interactions (PPIs) are critical regulatory events in physiology and pathology, and they represent an important target space for pharmacological intervention. However, targeting PPIs with small molecules is challenging owing to the large surface area involved in protein-protein binding and the lack of obvious small-molecule-binding pockets at many protein-protein interfaces. Nonetheless, successful examples of small-molecule modulators of PPIs have been growing in recent years. This article reviews some of the recent advances in the discovery of small-molecule regulators of PPIs that involve key oncogenic proteins. Our discussion focuses on the three key modes of action for these small-molecule modulators: orthosteric inhibition, allosteric regulation, and interfacial binding/stabilization. Understanding the opportunities and challenges of these diverse mechanisms will help guide future efforts in developing small-molecule modulators against PPIs.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-pharmtox-011613-140028
2014-01-06
2024-04-13
Loading full text...

Full text loading...

/content/journals/10.1146/annurev-pharmtox-011613-140028
Loading
/content/journals/10.1146/annurev-pharmtox-011613-140028
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error