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An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1

Thoreen CC, Kang SA, Chang JW, Liu Q, Zhang Jianming, Gao Y, Reichling LJ, Sim T, Sabatini DM, Gray NS · 2009 · Journal of Biological Chemistry · Atlas ID THO2009

What this study shows

Dropped a bombshell: rapamycin does NOT fully block mTORC1. Using Torin1 (which jams the active site directly), the authors showed rapamycin leaves important mTORC1 jobs running - notably 4E-BP1 phosphorylation and autophagy suppression. This reframed a decade of rapamycin experiments and launched the search for complete inhibitors.

Abstract

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The mammalian target of rapamycin (mTOR) kinase is the catalytic subunit of two functionally distinct complexes, mTORC1 and mTORC2, that coordinately promote cell growth, proliferation, and survival. Rapamycin is a potent allosteric mTORC1 inhibitor with clinical applications as an immunosuppressant and anti-cancer agent. Here we find that Torin1, a highly potent and selective ATP-competitive mTOR inhibitor that directly inhibits both complexes, impairs cell growth and proliferation to a far greater degree than rapamycin.

Read the full abstract on PubMed →

At a glance

Evidence type M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Mouse/human cells) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is.
Study type5 - Mechanistic / In Vitro
Model systemMouse/human cells
JournalJournal of Biological Chemistry
Year2009
Peer reviewedYes
Record last updated2026-08-22
SourceDOI 10.1074/jbc.M900301200 · PMID 19150980 · Free full text (PMC2658096)

Extracted findings

InterventionTorin1 (ATP-competitive mTOR inhibitor)
TargetmTORC1 (rapamycin-resistant outputs, 4E-BP)
ModelMouse/human cells
EffectTorin1 reveals rapamycin-resistant functions of mTORC1 (e.g. 4E-BP1 phosphorylation, autophagy)

In the Atlas

Related topics

Torin1RapamycinmTORC14E-BP1

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Cite this paper

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Thoreen, C. C., Kang, S. A., Chang, J. W., Liu, Q., Zhang Jianming, Gao, Y., Reichling, L. J., Sim, T., Sabatini, D. M., & Gray, N. S. (2009). An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.M900301200

@article{THO2009,
  author       = {Thoreen, C. C. and Kang, S. A. and Chang, J. W. and Liu, Q. and Zhang Jianming and Gao, Y. and Reichling, L. J. and Sim, T. and Sabatini, D. M. and Gray, N. S.},
  title        = {{An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1}},
  journal      = {Journal of Biological Chemistry},
  year         = {2009},
  doi          = {10.1074/jbc.M900301200},
  note         = {PMID: 19150980},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper. 

Barton, O. (2026). Oliver's mTOR Atlas (record THO2009) [Data set]. https://mtor-atlas.org/study/THO2009/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_THO2009,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record THO2009},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/THO2009/},
  doi          = {10.5281/zenodo.22059963}
}