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Departments of Medicinal Chemistry, Piramal Life Sciences Limited, 1 Nirlon, Off Western Express Highway, Goregaon (E) Mumbai, India

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Sanjay Kumar

† Author for correspondence

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Email the corresponding author at sanjay.kumar@piramal.com

Published Online:13 Oct 2010https://doi.org/10.4155/fmc.10.233

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Abstract

Mammalian target of rapamycin (mTOR) belongs to the atypical kinase family of phosphatidylinositol-3-kinase-related kinase and function as a master regulators of the switch between catabolic and anabolic metabolism. In the last decade mTOR has emerged as a therapeutic target for various diseases such as cancer, inflammation and metabolic disorders. mTOR plays a crucial role in the PI3K/AKT/PDK1 pathway. In this review we will provide an overview of both selective and nonselective mTOR inhibitors. Since rapamycin and rapalogs have been reviewed before, more emphasis has been placed on nonrapamycin-based small-molecule inhibitors and their modulation of mTOR selectivity. Recent efforts in obtaining mTOR-selective inhibitors have produced a range of compounds with more than 1000-fold selectivity over PI3K, but it is still a matter of debate whether an mTOR-selective inhibitor will be of more clinical significance over a PI3K/AKT/mTOR inhibitor.

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

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Vol. 2, No. 10

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Published online 13 October 2010

Published in print October 2010

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Financial & competing interests disclosure

The authors are employees of Piramal Life sciences Ltd. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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Recent advances in the discovery of small molecule mTOR inhibitors

Abstract

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