The Enigma of Rapamycin Dosage

The Enigma of Rapamycin Dosage

REVIEW| MARCH 06 2016

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Although we achieve the lower end of this range with periodic low dosing, whether it gets to the cancer tissues is less clear.

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from the paper:
PA [phosphatidic acid] binds mTOR in a manner that is competitive with and antagonistic to rapamycin […] rapamycin cannot bind to mTOR unless PA dissociates from the FRB domain of mTOR. A PA-based model for the differential sensitivity of mTORC1 and mTORC2 to rapamycin may trigger new routes of cancer therapy

Or anti-aging therapy, with higher mTORC1 inhibition without much mTORC2 inhibition.

The paper’s main conclusions:

The three problematic areas are the different doses of rapamycin required to: (i) achieve the same effect in different cell lines; (ii) suppress the phosphorylation of different mTORC1 substrates; and (iii) suppress mTORC1 and mTORC2. All three effects can be attributed, at least in part, to the interaction between mTOR and PA.

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