3-phosphoinositide-dependent Kinase 1 (PDK-1)
| 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. Feel free to contact us!
(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)