Pathway link TORIN-MTORC2
ATP-competitive mTOR inhibitors mTORC2
ATP-competitive mTOR inhibitors inhibits mTORC2.
mTORC1 and mTORC2 use the same ATP-binding pocket, so a drug that blocks the pocket hits both and cannot choose. That is thought to explain why this class of drugs causes more metabolic and immune side effects than rapamycin-type drugs, but the size of that effect has only been seen in cell studies and has not been measured in patients.
The conditions it holds under
Explains the metabolic and immunological toxicity of this class relative to rapalogs; the magnitude in patients is not established from these cell-line studies.
- Time it takes
- minutes
- Step
- direct (one molecule acts on the other)
- Measured in
- mammalian cells
- Where in the cell
- plasma membrane
- Reaches people?
- plausible in people, not shown directly
- How settled
- settled in the literature
Studies behind it
| Year | Evidence | Study |
|---|---|---|
| 2009 | M | An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1THO2009 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. |
| 2009 | M | Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2FEL2009 The parallel discovery to Thoreen 2009 (same year), from the Shokat lab. Their TORKinibs (PP242, PP30) block mTOR's active site, hitting both complexes and shutting down cap-dependent translation that rapamycin misses. Together these two papers established a whole new drug class beyond rapamycin. |
| 2010 | M | Effective and selective targeting of leukemia cells using a TORC1/2 kinase inhibitorJAN2010 The ATP-competitive TORC1/2 inhibitor PP242 selectively kills leukemia cells, with much weaker effects on the proliferation and function of normal lymphocytes. |
| 2011 | M | mTOR kinase inhibition causes feedback-dependent biphasic regulation of AKT signalingROD2011 mTOR kinase inhibition triggers feedback-dependent biphasic AKT reactivation, informing resistance. |
| 2009 | M | Ku-0063794 is a specific inhibitor of the mammalian target of rapamycin (mTOR)GAR2009 Ku-0063794 is a specific ATP-competitive mTOR inhibitor blocking mTORC1 and mTORC2. |
Points the other way
No study in the Atlas contradicts this link. That means none in this curated set, not none in the literature.
Who has checked this
- Checked by
- No researcher outside the project has checked this link yet.
- Curator sign-off
- Not signed off yet. This link was drafted with AI help and has not been reviewed link by link; treat it as a proposal until it is.
- Curated by
- Oliver Barton, with AI help for drafting; see how links are checked.
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