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The KRAS oncoprotein has topped medicinal chemists’ lists of undruggable targets for decades. Mutated in up to 25% of cancer cases, and associated with particularly poor disease prognoses, the therapeutic rationale for blockade of proliferative KRAS signalling is clear. But because the protein’s surface is smooth, with the exception of a GTP-binding pocket that holds on to its substrate too tightly to be displaced, drug hunters have struggled to find footholds for small-molecule drug candidates.