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Rapamycin and mTOR kinase inhibitors

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  • Published:
Journal of Chemical Biology

Abstract

Mammalian target of rapamycin (mTOR) is a protein kinase that controls cell growth, proliferation, and survival. mTOR signaling is often upregulated in cancer and there is great interest in developing drugs that target this enzyme. Rapamycin and its analogs bind to a domain separate from the catalytic site to block a subset of mTOR functions. These drugs are extremely selective for mTOR and are already in clinical use for treating cancers, but they could potentially activate an mTOR-dependent survival pathway that could lead to treatment failure. By contrast, small molecules that compete with ATP in the catalytic site would inhibit all of the kinase-dependent functions of mTOR without activating the survival pathway. Several non-selective mTOR kinase inhibitors have been described and here we review their chemical and cellular properties. Further development of selective mTOR kinase inhibitors holds the promise of yielding potent anticancer drugs with a novel mechanism of action.

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Acknowledgments

The authors’ research was supported by Carol M. Baldwin Breast Cancer Research Awards, and grants from the Department of Veterans Affairs and the National Institutes of Health DK62722. We greatly appreciate the expert graphical assistance of Jun Yong Choi.

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  1. Department of Medicine, Stony Brook University, Stony Brook, NY, 11794, USA

    Lisa M. Ballou & Richard Z. Lin

  2. Department of Physiology and Biophysics and the Institute of Molecular Cardiology, Stony Brook University, Stony Brook, NY, 11794, USA

    Richard Z. Lin

  3. Department of Veterans Affairs Medical Center, Northport, NY, 11768, USA

    Richard Z. Lin

  4. Department of Medicine, Division of Hematology/Oncology, Stony Brook University, Stony Brook, NY, 11794-8151, USA

    Richard Z. Lin

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Ballou, L.M., Lin, R.Z. Rapamycin and mTOR kinase inhibitors. J Chem Biol 1, 27–36 (2008). https://doi.org/10.1007/s12154-008-0003-5

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