Article
Small molecule binding sites on the Ras:SOS complex can be exploited for inhibition of Ras activation.
Journal of medicinal chemistry - 12 Mar 2015
Winter Jon J G, Anderson Malcolm, Blades Kevin, Brassington Claire, Breeze Alexander L, Chresta Christine, Embrey Kevin, Fairley Gary, Faulder Paul, Finlay M Raymond V, Kettle Jason G, Nowak Thorsten, Overman Ross, Patel S Joe, Perkins Paula, Spadola Loredana, Tart Jonathan, Tucker Julie A, Wrigley Gail
Abstract excerpt
Constitutively active mutant KRas displays a reduced rate of GTP hydrolysis via both intrinsic and GTPase-activating protein-catalyzed mechanisms, resulting in the perpetual activation of Ras pathways. We describe a fragment screening campaign using X-ray crystallography that led to the discovery of three fragment binding sites on the Ras:SOS complex. The identification of tool compounds binding at each of these...
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