Oliver's mTOR Atlas Evidence Platform
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Pathway link BISTERIC-MTORC1

Bi-steric mTORC1-selective inhibitors mTORC1

Bi-steric mTORC1-selective inhibitors inhibits mTORC1.

A two-part drug grips mTORC1 at two places at once, which blocks it more completely than rapamycin-type drugs. So far only a first safety trial in people with advanced tumours has reported on it.

A bivalent molecule engages an FKBP12-dependent site and the active site simultaneously, producing deeper mTORC1 inhibition than a rapalog while sparing mTORC2.

The conditions it holds under

Phase 1 in advanced solid tumours – a safety and pharmacodynamic result, not an efficacy verdict. Directness is graded indirect because, like rapalogs, the mechanism requires FKBP12. Consensus is emerging: one trial.

Time it takes
hours
Step
indirect (through steps not drawn here)
Measured in
human
Where in the cell
lysosome
Reaches people?
plausible in people, not shown directly
How settled
emerging, few independent studies

Studies behind it

YearEvidenceStudy
2025 H The Bi-steric, mTORC1-Selective Inhibitor, RMC-5552, in Advanced Solid Tumors: A Phase 1 TrialSCH2025 First-in-human, open-label dose-escalation trial (n=57, advanced solid tumors, no comparator arm) of a bi-steric mTORC1-selective inhibitor. Treatment-related hyperglycemia was low (4%) and not dose-limiting, alongside a 64% disease control rate. Because the trial was uncontrolled and made no head-to-head comparison against rapamycin or an ATP-site inhibitor, this is encouraging early clinical evidence consistent with the hypothesis that sparing mTORC2 reduces metabolic toxicity -- it does not establish mTORC2 sparing as the cause.

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.

“Inhibits” describes the effect on the target's activity, not on how much of it there is.

“How settled” describes how far researchers in the field agree. It is not the same as the sign-off above, which only says whether a named curator has checked this page.

If this link rests on your own work: a click on “This looks right” below, or a short note through “Report an error”, helps us more than anything else on this page.

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