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  • An orally available inhibitor of the oncogenic KRAS substitution mutation, G12C, with potential antineoplastic activity. Upon oral administration, LY3499446 targets and covalently binds to cytosine 12 within the switch II pocket of GDP-bound KRAS G12C, thereby inhibiting mutant KRAS-dependent signaling. KRAS, a member of the RAS family of oncogenes, serves an important role in cell signaling, division and differentiation. Mutations of KRAS may induce constitutive signal transduction leading to tumor cell growth, proliferation, invasion, and metastasis.
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