Discovery and biological activity of computer-assisted drug designed Akt pathway inhibitors
| Autor: | Nne E. Uko, J. Phillip Bowen, Diane F. Matesic, Osman F. Güner, Lillie M.A. Barnett |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Models Molecular Cell signaling Lung Neoplasms Clinical Biochemistry Pharmaceutical Science Inhibitory postsynaptic potential 01 natural sciences Biochemistry 03 medical and health sciences chemistry.chemical_compound Alkaloids Cell Line Tumor Drug Discovery Solenopsin Humans Phosphorylation Molecular Biology Protein kinase B Protein Kinase Inhibitors PI3K/AKT/mTOR pathway Organic Chemistry Biological activity 0104 chemical sciences Enzyme Activation 010404 medicinal & biomolecular chemistry 030104 developmental biology chemistry Drug Design Cancer research Molecular Medicine Pharmacophore Lead compound Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Bioorganicmedicinal chemistry letters. 28(19) |
| ISSN: | 1464-3405 |
| Popis: | The P13K/Akt pathway is a growth-regulating cellular signaling pathway that is over-activated in numerous human cancers. A novel series of Akt pathway inhibitors were identified using iterative pharmacophore modeling, energy-based calculations, and property predictions of known Akt inhibitors. Inhibitory effects on activation of Akt and growth of human neoplastic cells are reported. Results show variable inhibitory effects of three selected compounds on Akt phosphorylation at a key activation site, and on proliferation of tumorigenic cells. We identify one lead compound with potent inhibitory activity on both human carcinoma cell proliferation and Akt activation. |
| Databáze: | OpenAIRE |
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