PHT-427 is a novel dual inhibitor of 3-phosphoinositide dependent protein kinase 1 (PDK1) and Akt (protein kinase B) [3
]. The original identification of PHT-427 (compound 14) as an Akt inhibitor is described in [1
] where it is shown to bind to the pleckstrin homology (PH) domain of Akt, not to the catalytic ATP binding site. PDK1 activates Akt by phosphorylating Thr308
in Akt's kinase domain.
The PDK1/Akt signaling pathway plays a key role in cancer cell growth, survival, and tumour angiogenesis and represents a promising target for oncology therapeutics [2