) The objective of the Cell Fluorescent Biosensor Core (Core E) is to provide primary, multiparameter, cellular, high throughput systems (HTS) for the Projects and Core A described in this NCDDG application. The key instrument is a Cellomics Array Scan, which will also provide a important link between compound sources (namely the NCI compound library and the compounds from the Combinatorial Chemistry Core A) and all of the target screening activities directed toward identifying cancer therapies. There has been an explosive growth in our understanding of the human genome, which has radically enhanced the number of molecular targets for potentially efficacious pharmacological entities. Many potential interesting molecular targets are regulated not only by expression levels but also by their subcellular or spatial localization. Agents that selectively affect the spatial localization of cancer related molecular targets have not been carefully investigated. The underlying hypothesis upon which work by Core E is based is that identifying agents that affect the translocation of cancer-related proteins will yield small molecules with unique potential as anticancer drugs. To achieve this goal in a timely manner, we have incorporated robotic-based, multiparametric, detection systems that will permit rapid evaluation of newly identified biological targets and synthesized chemical entities in intact living cells.
The aims of the Core service are: 1) To identify compounds having significant effects on the spatial location of targeted cell cycle progression and apoptosis-associated proteins, 2) To identify compounds having significant effects on apoptosis, 3) To determine the optimal drug concentration for prioritized compounds and, 4) To determine if prioritized agents have synergistic or antagonist effects with representative conventional anticancer drugs.
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| Leone, Marilisa; Barile, Elisa; Vazquez, Jesus et al. (2010) NMR-based design and evaluation of novel bidentate inhibitors of the protein tyrosine phosphatase YopH. Chem Biol Drug Des 76:10-6 |
| Ihle, Nathan T; Powis, Garth (2010) The biological effects of isoform-specific PI3-kinase inhibition. Curr Opin Drug Discov Devel 13:41-9 |
| Koul, Dimpy; Shen, Ruijun; Kim, Yong-Wan et al. (2010) Cellular and in vivo activity of a novel PI3K inhibitor, PX-866, against human glioblastoma. Neuro Oncol 12:559-69 |
| Ihle, Nathan T; Powis, Garth (2010) Inhibitors of phosphatidylinositol-3-kinase in cancer therapy. Mol Aspects Med 31:135-44 |
| Ihle, Nathan T; Powis, Garth (2009) Take your PIK: phosphatidylinositol 3-kinase inhibitors race through the clinic and toward cancer therapy. Mol Cancer Ther 8:1-9 |
| Tomko Jr, Robert J; Azang-Njaah, Ndang N; Lazo, John S (2009) Nitrosative stress suppresses checkpoint activation after DNA synthesis inhibition. Cell Cycle 8:299-305 |
| Gaitonde, Supriya; De, Surya K; Tcherpakov, Marianna et al. (2009) BI-69A11-mediated inhibition of AKT leads to effective regression of xenograft melanoma. Pigment Cell Melanoma Res 22:187-95 |
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