Small Molecule Binding Sites on the Ras:SOS Complex Can Be Exploited for Inhibition of Ras Activation was written by 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. And the article was included in Journal of Medicinal Chemistry in 2015.Application of 957120-53-5 The following contents are mentioned in the article:
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 crystallog. 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 sites allowed exploration of two new approaches to Ras pathway inhibition by stabilizing or covalently modifying the Ras:SOS complex to prevent the reloading of Ras with GTP. Initially, we identified ligands that bound reversibly to the Ras:SOS complex in two distinct sites, but these compounds were not sufficiently potent inhibitors to validate our stabilization hypothesis. We conclude by demonstrating that covalent modification of Cys118 on Ras leads to a novel mechanism of inhibition of the SOS-mediated interaction between Ras and Raf and is effective at inhibiting the exchange of labeled GDP in both mutant (G12C and G12V) and wild type Ras. This study involved multiple reactions and reactants, such as (3-Carbamoyl-5-chlorophenyl)boronic acid (cas: 957120-53-5Application of 957120-53-5).
(3-Carbamoyl-5-chlorophenyl)boronic acid (cas: 957120-53-5) belongs to organic chlorides. Organic chlorides can be used in production of: PVC, pesticides, chloromethane, teflon, insulators. The haloform reaction, using chlorine and sodium hydroxide, is also able to generate alkyl halides from methyl ketones, and related compounds. Chloroform was formerly produced thus.Application of 957120-53-5
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Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics