The PI3K/PDK-1/Akt signaling cascade represents a convergence point for a plethora of receptor tyrosine kinase and cytokine-mediated pathways that regulate cell proliferation and survival and offer a framework to account for the ability of many extracellular trophic factors to maintain cell survival.

Deregulation of this signaling cascade due to constitutive growth factor-receptor activation and/or PTEN mutations results in Akt up-regulation, which  subsequently promotes tumor invasiveness, angiogenesis, and progression. Thus, PDK-1/Akt signaling inhibitors are of translational relevance for development into useful chemotherapeutic or chemopreventive agents. (Zhu J, Huang JW, Tseng PH, Yang YT, Fowble J, Shiau CW, Shaw YJ, Kulp SK, Chen CS. From the cyclooxygenase-2 inhibitor celecoxib to a novel class of 3-phosphoinositide-dependent protein kinase-1 inhibitors. Cancer Res. 2004 Jun 15;64(12):4309-18)

 The target-focused libraries was generated using receptor-based virtual screening (docking) of the 370 000 compounds stock collection (Life Chemicals Collection 300 000 compounds and Otava Collection 70 000 compounds). In this case detection of H-bonding between ligand and key PDK-1 residues (Ala162) was carried out.