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KRAS INHIBITORS

Hitting the hotspots

Despite well-established tumorigenic roles of KRAS mutants, targeting their smooth surfaces was a challenge, which was overcome through the development of G12C-specific covalent inhibitors. A new study shows that optimizing non-covalent interactions with a cryptic pocket produces remarkable potency for another hotspot mutation.

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Fig. 1: Flexible switch I/II and switch II pockets targeted in KRAS.

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Correspondence to Mitsuhiko Ikura.

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Marshall, C.B., Ikura, M. Hitting the hotspots. Nat Chem Biol 18, 578–579 (2022). https://doi.org/10.1038/s41589-022-01000-y

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