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 proceedingChapter

17 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 languageEnglish
Title of host publicationMethods in Molecular Biology
Pages447-460
Number of pages14
Volume821
DOIs
Publication statusPublished - 2012 Jan 2
Externally publishedYes

Publication series

NameMethods in Molecular Biology
Volume821
ISSN (Print)10643745

Fingerprint

Sirolimus
Adenosine Triphosphate
Drug Design
Metabolic Diseases
Antineoplastic Agents
Neoplasms

Keywords

  • Akt
  • mTOR
  • mTORC1
  • mTORC2
  • PI3K
  • PIKK
  • Rapamycin
  • Torin1

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

Cite this

Liu, Q., Kang, S. A., Thoreen, C. C., Hur, W., Wang, J., Chang, J. W., ... Gray, N. S. (2012). Development of ATP-competitive mTOR inhibitors. In Methods in Molecular Biology (Vol. 821, pp. 447-460). (Methods in Molecular Biology; Vol. 821). https://doi.org/10.1007/978-1-61779-430-8_29

Development of ATP-competitive mTOR inhibitors. / Liu, Qingsong; Kang, Seong A.; Thoreen, Carson C.; Hur, Wooyoung; Wang, Jinhua; Chang, Jae Won; Markhard, Andrew; Zhang, Jianming; Sim, Taebo; Sabatini, David M.; Gray, Nathanael S.

Methods in Molecular Biology. Vol. 821 2012. p. 447-460 (Methods in Molecular Biology; Vol. 821).

Research output: Chapter in Book/Report/Conference proceedingChapter

Liu, Q, Kang, SA, Thoreen, CC, Hur, W, Wang, J, Chang, JW, Markhard, A, Zhang, J, Sim, T, Sabatini, DM & Gray, NS 2012, Development of ATP-competitive mTOR inhibitors. in Methods in Molecular Biology. vol. 821, Methods in Molecular Biology, vol. 821, pp. 447-460. https://doi.org/10.1007/978-1-61779-430-8_29
Liu Q, Kang SA, Thoreen CC, Hur W, Wang J, Chang JW et al. Development of ATP-competitive mTOR inhibitors. In Methods in Molecular Biology. Vol. 821. 2012. p. 447-460. (Methods in Molecular Biology). https://doi.org/10.1007/978-1-61779-430-8_29
Liu, Qingsong ; Kang, Seong A. ; Thoreen, Carson C. ; Hur, Wooyoung ; Wang, Jinhua ; Chang, Jae Won ; Markhard, Andrew ; Zhang, Jianming ; Sim, Taebo ; Sabatini, David M. ; Gray, Nathanael S. / Development of ATP-competitive mTOR inhibitors. Methods in Molecular Biology. Vol. 821 2012. pp. 447-460 (Methods in Molecular Biology).
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