Development of ATP-competitive mTOR inhibitors

Qingsong Liu; Seong A. Kang; Carson C. Thoreen; Wooyoung Hur; Jinhua Wang; Jae Won Chang; Andrew Markhard; Jianming Zhang; Taebo Sim; David M. Sabatini; Nathanael S. Gray

doi:10.1007/978-1-61779-430-8_29

Development of ATP-competitive mTOR inhibitors

Qingsong Liu, Seong A. Kang, Carson C. Thoreen, Wooyoung Hur, Jinhua Wang, Jae Won Chang, Andrew Markhard, Jianming Zhang, Taebo Sim, David M. Sabatini, Nathanael S. Gray

Research output: Chapter in Book/Report/Conference proceeding › Chapter

36 Citations (Scopus)

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.

Original language	English
Title of host publication	mTOR
Subtitle of host publication	Methods and Protocols
Editors	Thomas Weichhart
Pages	447-460
Number of pages	14
DOIs	https://doi.org/10.1007/978-1-61779-430-8_29
Publication status	Published - 2012

Publication series

Name	Methods in Molecular Biology
Volume	821
ISSN (Print)	1064-3745

Keywords

Akt
PI3K
PIKK
Rapamycin
Torin1
mTOR
mTORC1
mTORC2

ASJC Scopus subject areas

Molecular Biology
Genetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1007/978-1-61779-430-8_29

Cite this

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AU - Kang, Seong A.

AU - Thoreen, Carson C.

AU - Hur, Wooyoung

AU - Wang, Jinhua

AU - Chang, Jae Won

AU - Markhard, Andrew

AU - Zhang, Jianming

AU - Sim, Taebo

AU - Sabatini, David M.

AU - Gray, Nathanael S.

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KW - Akt

KW - PI3K

KW - PIKK

KW - Rapamycin

KW - Torin1

KW - mTOR

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KW - mTORC2

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Development of ATP-competitive mTOR inhibitors

Abstract

Publication series

Keywords

ASJC Scopus subject areas

UN SDGs

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