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Nat Rev Drug Discov. 2011 Oct 31;10(11):868-80. doi: 10.1038/nrd3531.

Rapamycin passes the torch: a new generation of mTOR inhibitors.

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1
Biozentrum, University of Basel, CH4056 Basel, Switzerland.

Abstract

Mammalian target of rapamycin (mTOR) is an atypical protein kinase that controls growth and metabolism in response to nutrients, growth factors and cellular energy levels, and it is frequently dysregulated in cancer and metabolic disorders. Rapamycin is an allosteric inhibitor of mTOR, and was approved as an immuno-suppressant in 1999. In recent years, interest has focused on its potential as an anticancer drug. However, the performance of rapamycin and its analogues (rapalogues) has been undistinguished despite isolated successes in subsets of cancer, suggesting that the full therapeutic potential of targeting mTOR has yet to be exploited. A new generation of ATP-competitive inhibitors that directly target the mTOR catalytic site display potent and comprehensive mTOR inhibition and are in early clinical trials.

PMID:
22037041
DOI:
10.1038/nrd3531
[Indexed for MEDLINE]

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