PS210 is a potent and selective activator of PDK1 (Kd: 3 μM), specifically targeting the PIF-binding pocket of PDK1 without affecting other protein kinases such as S6K, PKB/Akt, or GSK3. Its prodrug, PS423, serves as a substrate-selective inhibitor of PDK1 in cells, inhibiting the phosphorylation and activation of S6K.

PDK1:(kd)3 μM

PS210 stabilized the residue Arg131 when PS210 causes stabilization of PDK1 to the temperature gradient, located opposite to the helix a-B at the other extreme of the helix a-C. So, the residues forming part of the phosphate-binding site appear to be a fixed point that allows for the relative movement of the helices in the process of PDK1 activation[1].