Biological ActivityKRas/son of sevenless 1 (SOS1) interaction inhibitor. Binds within nucleotide binding pocket of KRas (Kd values are 106 - 176 nM for wild type KRas and various KRas mutants). Inhibits nucleotide binding to KRas in a concentration dependent manner. Displays cytotoxicity in KRas-driven cancer cell lines and inhibits downstream ERK-MAPK signaling. Cell permeable.
(Modifications: Arg-1 = N-terminal Ac, X = (S)-2-(4-pentenyl)alanine, X-7 and X-11 stapled together with a double bond)
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Direct inhibition of oncogenic KRAS by hydrocarbon-stapled SOS1 helices.
Leshchiner et al.
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