PHT-427 is a dual Akt and PDPK1 inhibitor (high affinity binding for the PH domains of Akt and PDPK1) with Ki of 2.7 μM and 5.2 μM, respectively.

PH-427 is a pleckstrin homology domain inhibitor to Akt/PDPK1. PH-427 significantly reduces phospho-Ser241-PDPK1 phospho-Thr308-Akt in PC-3 prostate cancer cells at 10 μM, which shows that PHT-427 could inhibit both Akt and PDPK1. PHT-427 also inhibits translocation of the Akt and PDPK1 PH domains in plasma membrane. PHT-427 induces apoptosis and inhibits AKT phosphorylation with IC50 of 8.6 μM (in BxPC-3 cells), which mainly on its Ser473 residue and less strongly on Thr308 residue without affecting total Akt protein expression. PHT-427 also shows antiproliferation in Panc-1 cells with IC50 of 65 μM.