3-phosphoinositide-dependent Kinase 1 (PDK-1)
 Ligand in PDK-1 active site
 Ligand in PDK-1 active site. Docking example from OTAVAchemicals 3-phosphoinositide-dependent
kinase-1 (PDK-1) focused library.
The detection of H-bonding between ligand and key PDK-1 residues (Ala162) was used for the library preparation.

The phosphatidylinositol 3'-kinase/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 offers a framework to account for the ability of many extracellular trophic factors to maintain cell survival. Dysregulation 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.

The focused libraries, including docking scores and drug-like properties, are available on request.

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(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)