@inbook{afe0f4e3593d478e900944b6fedde159,
title = "Development of ATP-competitive mTOR inhibitors",
abstract = "The mammalian Target of Rapamycin (mTOR)-mediated signaling transduction pathway has been observed to be deregulated in a wide variety of cancer and metabolic diseases. Despite extensive clinical development efforts, the well-known allosteric mTOR inhibitor rapamycin and structurally related rapalogs have failed to show significant single-agent antitumor efficacy in most types of cancer. This limited clinical success may be due to the inability of the rapalogs to maintain a complete blockade mTOR-mediated signaling. Therefore, numerous efforts have been initiated to develop ATP-competitive mTOR inhibitors that would block both mTORC1 and mTORC2 complex activity. Here, we describe our experimental approaches to develop Torin1 using a medium throughput cell-based screening assay and structure-guided drug design.",
keywords = "Akt, PI3K, PIKK, Rapamycin, Torin1, mTOR, mTORC1, mTORC2",
author = "Qingsong Liu and Kang, {Seong A.} and Thoreen, {Carson C.} and Wooyoung Hur and Jinhua Wang and Chang, {Jae Won} and Andrew Markhard and Jianming Zhang and Taebo Sim and Sabatini, {David M.} and Gray, {Nathanael S.}",
year = "2012",
doi = "10.1007/978-1-61779-430-8_29",
language = "English",
isbn = "9781617794292",
series = "Methods in Molecular Biology",
pages = "447--460",
editor = "Thomas Weichhart",
booktitle = "mTOR",
}
