PDK1-IN-RS2 is a mimic of peptide docking motif (PIFtide) and is a substrate-selective PDK1 inhibitor with a Kd of 9 μM. PDK1-IN-RS2 suppresses the activation of the downstream kinases S6K1 by PDK1[1].
PDK1-IN-RS2 stimulates the catalytic activity of PDK1 toward a peptide substrate by sixfold. The sulfonyl group of PDK1-IN-RS2 interacts with Arg131 through a salt bridge, because the sulfonamide is likely ionized under the crystallization conditions[1].