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Selective inhibition of mutant Ras protein through covalent binding.

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.