Your comments, thoughts, opinions?
Would having a constant raperymicin/sirolimus blood levels of 5-15ng/ml effect mTORC1 and not mTORC2?
You would definitely be triggering mTOR2 side effects at these levels. In the literature, “trough” levels of 5-15 ng/ml are a commonly observed therapeutic target in cancer/transplant studies.
“Sirolimus treatment was initiated with a loading dose of 6 mg by mouth on day 1 followed by 2 mg by mouth daily. Sirolimus is FDA approved for use after kidney transplantation and this is the standard dose used in the kidney transplant population. The dose was then adjusted to maintain a target blood level of 3–9 ng/ml for the first 16 weeks. After week 16, the dose of sirolimus was increased to a target level of 9–15 ng/ml unless there was evidence for a partial response or complete response by kidney MRI. There was no change in dose for those with a partial response or complete response at week 16. Trough sirolimus levels were checked every 8–12 weeks (at 24 weeks, 32 weeks, 40 weeks, and 52 weeks) in all patients until the 12-month (week 52) study visit. If the sirolimus dose was below target, the dose was increased by 1– 2 mg until the target trough level was achieved. Sirolimus levels were checked every 2–3 weeks while the dose was adjusted”
Toxicity data for this study
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