Hormonal
The novel rapamycin analog DL001 selectively inhibits mTORC1 in vivo without disrupting glucose or lipid homeostasis, unlike conventional rapamycin which causes metabolic side effects via mTORC2 inhibition.
This research identifies a specific compound (DL001) that inhibits the mTORC1 pathway without causing the metabolic side effects (like high blood sugar and bad cholesterol) seen with standard rapamycin. While promising for treating age-related diseases and tuberous sclerosis in future human trials, it is not currently available for general use. The key takeaway is that selective mTORC1 inhibition may be a viable strategy to avoid metabolic disruption.
DL001 inhibits mTORC1 in cell culture lines and in vivo in C57BL/6J mice, in which DL001 inhibits mTORC1 signaling without impairing glucose homeostasis and with substantially reduced or no side effects on lipid metabolism and the immune system.
Why this rating
Strong in vivo mouse data with clear mechanistic distinction from rapamycin, but lacks human clinical trial data.
Source
A novel rapamycin analog is highly selective for mTORC1 in vivo
Katherine H. Schreiber et al. · Nature Communications · 2019
DOI 10.1038/s41467-019-11174-0
More from this paper
- DL001 reduces the immunosuppressive effects of mTOR inhibition compared to rapamycin, specifically preserving more T cell and Treg populations.Good
- DL001 effectively suppresses hyperactive mTORC1 signaling in cells lacking a functional TSC (Tuberous Sclerosis Complex), restoring normal gene expression.Good
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