New Inhibitors Target mTOR for Cancer Treatment
Author Information
Author(s): Feldman Morris E, Apsel Beth, Uotila Aino, Loewith Robbie, Knight Zachary A, Ruggero Davide, Shokat Kevan M
Primary Institution: University of California San Francisco
Hypothesis
Can new active-site inhibitors of mTOR effectively target both mTORC1 and mTORC2 to improve cancer treatment outcomes?
Conclusion
The study found that new mTOR inhibitors, TORKinibs, are more effective than rapamycin in blocking cell proliferation and inhibiting protein synthesis.
Supporting Evidence
- PP242 and PP30 inhibit mTOR in vitro with IC50 values of 8 nM and 80 nM, respectively.
- PP242 and PP30 inhibit insulin-stimulated phosphorylation of Akt at S473.
- PP242 was more effective than rapamycin at blocking cell proliferation in primary cells.
Takeaway
Scientists created new drugs that can stop a protein called mTOR from helping cancer cells grow, and these drugs work better than an old one called rapamycin.
Methodology
The study used two novel mTOR kinase domain inhibitors (PP242 and PP30) to investigate mTOR signaling in cells and animals.
Limitations
The effects of mTOR inhibition on different tissues and the potential off-target effects of the inhibitors were not fully explored.
Statistical Information
P-Value
p<0.001
Statistical Significance
p<0.001
Digital Object Identifier (DOI)
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