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Small‐molecule inhibition of the interaction between the KRas oncoprotein and the chaperone PDE6δ impairs KRas spatial organization and signaling in cells. However, despite potent binding in vitro (KD<10 nm), interference with Ras signaling and growth inhibition require 5–20 μm compound concentrations. We demonstrate that these findings can be explained by fast release of high‐affinity inhibitors...
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