Rapamycin and mTOR kinase inhibitors

LM Ballou, RZ Lin - Journal of chemical biology, 2008 - Springer
LM Ballou, RZ Lin
Journal of chemical biology, 2008Springer
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 …
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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