Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 24, Issue 3, Pages 835-838Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2013.12.081
Keywords
Virtual screening; mTOR; Docking; Kinase inhibitor; Anticancer agents
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Funding
- National Research Foundation of Korea (NRF)
- Ministry of Education, Science and Technology [NRF-2011-0022858, 2010-0022179, 0016436]
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Mammalian target of rapamycin (mTOR) is a promising target for the development of anticancer medicines. Here, we report the first example for a successful application of the structure-based virtual screening to identify new mTOR inhibitors. Using the scoring function improved by implementing the ligand solvation effects on protein-ligand association, six novel mTOR inhibitors are found with IC50 values ranging from 8 to 60 mu M. Because these new inhibitors are also computationally screened for having desirable physicochemical properties as a drug candidate, they deserve consideration for further development by structure-activity relationship studies to optimize the inhibitory and anticancer activities. Structural features relevant to the stabilization of the inhibitors in the ATP-binding site of mTOR are addressed in detail. (C) 2013 Elsevier Ltd. All rights reserved.
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