Abstract
The mammalian Target of Rapamycin (mTOR)-mediated signaling transduction pathway has been observed to be deregulated in a wide variety of cancer and metabolic diseases. Despite extensive clinical development efforts, the well-known allosteric mTOR inhibitor rapamycin and structurally related rapalogs have failed to show significant single-agent antitumor efficacy in most types of cancer. This limited clinical success may be due to the inability of the rapalogs to maintain a complete blockade mTOR-mediated signaling. Therefore, numerous efforts have been initiated to develop ATP-competitive mTOR inhibitors that would block both mTORC1 and mTORC2 complex activity. Here, we describe our experimental approaches to develop Torin1 using a medium throughput cell-based screening assay and structure-guided drug design.
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Acknowledgements
We thank Life Technologies Corporation for SelectScreen® Kinase Profiling Service and Ambit Bioscience for performing KinomeScanTM profiling. We also thank SAI Advantium Pharma Limited Inc. (India) for the pharmacokinetic study.
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Liu, Q. et al. (2012). Development of ATP-Competitive mTOR Inhibitors. In: Weichhart, T. (eds) mTOR. Methods in Molecular Biology, vol 821. Humana Press. https://doi.org/10.1007/978-1-61779-430-8_29
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DOI: https://doi.org/10.1007/978-1-61779-430-8_29
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