Current status of the development of Ras inhibitors

J Biochem. 2015 Aug;158(2):91-9. doi: 10.1093/jb/mvv060. Epub 2015 Jun 22.


Despite the importance of ras as driver genes in many cancers, clinically effective anti-cancer drugs targeting their products, Ras, have been unavailable so far, which was in part ascribable to the apparently 'undruggable' nature of their tertiary structures. Nonetheless, recent studies in academia and industry have identified novel surface pockets accepting small-molecule ligands in both their active GTP-bound and inactive GDP-bound forms (Ras•GTP and Ras•GDP, respectively), which has led to a surge of investigations into the discovery of Ras-specific inhibitors particularly by utilizing their structural information for structure-based drug design (SBDD). We have been developing Ras inhibitors by SBDD targeting a novel conformation of Ras•GTP called state 1, possessing 'druggable' surface pockets, which emerges from the conformational dynamics. In this article, we will survey Ras functions from the structural biological point of view and summarize the current status of the development of Ras inhibitors including our own.

Keywords: NMR; Ras; X-ray crystallography; anti-cancer drugs; drug design; structure-based.

Publication types

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

MeSH terms

  • Animals
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Models, Molecular
  • Protein Binding / drug effects
  • Signal Transduction / drug effects
  • ras Proteins / antagonists & inhibitors*
  • ras Proteins / chemistry
  • ras Proteins / metabolism


  • Enzyme Inhibitors
  • ras Proteins