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Overview
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Background
Torin 1, a tricyclic benzonaphthyridinone, is a potent and selective inhibitor of the mammalian target of rapamycin (mTOR) kinase, which is the catalytic subunit of two functionally distinct complexes and plays a pivotal role in the regulation of cell growth, proliferation and survival. Torin 1 directly inhibits the two mTOR-containing complexes, mTORC1 and mTORC2, through an ATP-competitive mechanism with half maximal inhibitory concentration IC50 of 2 nM and 10 nM respectively. Torin 1 has been found to impair cell growth and proliferation through a mechanism involving mTORC1 inhibition other than mTORC2 inhibition, in which the rapamycin-resistant functions of mTORC1 is suppressed.
[1]Thoreen CC1, Kang SA, Chang JW, Liu Q, Zhang J, Gao Y, Reichling LJ, Sim T, Sabatini DM, Gray NS. An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1. J Biol Chem. 2009 Mar 20;284(12):8023-32. doi: 10.1074/jbc.M900301200. Epub 2009 Jan 15.
[2]Liu Q1, Chang JW, Wang J, Kang SA, Thoreen CC, Markhard A, Hur W, Zhang J, Sim T, Sabatini DM, Gray NS. Discovery of 1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo
[h][1,6]naphthyridin-2(1H)-one as a highly potent, selective mammalian target of rapamycin (mTOR) inhibitor for the treatment of cancer. J Med Chem. 2010 Oct 14;53(19):7146-55. doi: 10.1021/jm101144f.
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