title: Selective inhibition of mutant Ras protein through covalent binding.
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.
authors.affiliation: Discovery Chemistry, Genentech, Inc., One DNA Way, South San Francisco, CA 94080 (USA). rudolph.joachim@gene.com.
authors.forename: Joachim
authors.initials: J
authors.lastname: Rudolph
authors.forename: David
authors.initials: D
authors.lastname: Stokoe
mesh_terms: D001665:Binding Sites; D006801:Humans; D050505:Mutant Proteins / Q000378:metabolism*; D015398:Signal Transduction; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D050505:Mutant Proteins; D018631:ras Proteins
keywords: Ras mutations; cancer; drug design; inhibitors