Article
Selective and noncovalent targeting of RAS mutants for inhibition and degradation.
Nature communications - 11 May 2021
Teng Kai Wen, Tsai Steven T, Hattori Takamitsu, Fedele Carmine, Koide Akiko, Yang Chao, Hou Xuben, Zhang Yingkai, Neel Benjamin G, O'Bryan John P, Koide Shohei
Abstract excerpt
Activating mutants of RAS are commonly found in human cancers, but to date selective targeting of RAS in the clinic has been limited to KRAS(G12C) through covalent inhibitors. Here, we report a monobody, termed 12VC1, that recognizes the active state of both KRAS(G12V) and KRAS(G12C) up to 400-times more tightly than wild-type KRAS. The crystal structures reveal that 12VC1 recognizes the mutations through a...
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