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G12Si-1 is a selective, covalent K-Ras(G12S) inhibitor that inhibits K-Ras(G12S) oncogenic signaling. On mutant serine residues, G12Si-1 binds K-Ras(G12S) well.G12Si-1 may also be able to impede Sos-catalyzed exchange and inhibit EDTA-facilitated exchange rates, thereby affecting the nucleotide cycle of K-Ras.