Selective inhibition of mutant Ras protein through covalent binding

Angew Chem Int Ed Engl. 2014 Apr 7;53(15):3777-9. doi: 10.1002/anie.201400233. Epub 2014 Mar 3.

Abstract

One of the first oncogenes to be discovered and one of the most prevalently mutated tumor genes is Ras. Shokat et al. and Gray et al. have succeeded in discovering allosteric inhibitors and inhibitory nucleotide analogues, respectively, of K-Ras proteins that covalently and selectively bind G12C-mutant K-Ras. These strategies of specifically targeting a mutant form of Ras may offer an opportunity for cancer-selective therapies that spare normal tissue.

Keywords: Ras mutations; cancer; drug design; inhibitors.

MeSH terms

  • Binding Sites
  • Humans
  • Mutant Proteins / metabolism*
  • Signal Transduction
  • ras Proteins / metabolism*

Substances

  • Mutant Proteins
  • ras Proteins