Vidovic, T.; Dakhovnik, A.; Hrabovskyi, O.; MacArthur, M.R.; Ewald, C.Y. AI-Predicted mTOR Inhibitor Reduces Cancer Cell Proliferation and Extends the Lifespan of C. elegans. Int. J. Mol. Sci.2023, 24, 7850.
Vidovic, T.; Dakhovnik, A.; Hrabovskyi, O.; MacArthur, M.R.; Ewald, C.Y. AI-Predicted mTOR Inhibitor Reduces Cancer Cell Proliferation and Extends the Lifespan of C. elegans. Int. J. Mol. Sci. 2023, 24, 7850.
Vidovic, T.; Dakhovnik, A.; Hrabovskyi, O.; MacArthur, M.R.; Ewald, C.Y. AI-Predicted mTOR Inhibitor Reduces Cancer Cell Proliferation and Extends the Lifespan of C. elegans. Int. J. Mol. Sci.2023, 24, 7850.
Vidovic, T.; Dakhovnik, A.; Hrabovskyi, O.; MacArthur, M.R.; Ewald, C.Y. AI-Predicted mTOR Inhibitor Reduces Cancer Cell Proliferation and Extends the Lifespan of C. elegans. Int. J. Mol. Sci. 2023, 24, 7850.
Abstract
The mechanistic target of rapamycin (mTOR) kinase is one of the top drug targets for promoting health and lifespan extension. Besides rapamycin, only a few other mTOR inhibitors have been developed and shown their ability to slow aging. We used machine learning to predict novel small molecules targeting mTOR. We selected one small molecule, TKA001, based on in-silico predictions of a high on-target probability, low toxicity, favorable physicochemical properties, and preferable ADMET profile. We confirmed TKA001 binding in silico by molecular docking. TKA001 potently inhibits both TOR complex 1 and 2 downstream signaling in vitro. Furthermore, TKA001 inhibits human cancer cell proliferation in vitro and extended the lifespan of C. elegans, suggesting that TKA001 can slow aging in vivo.
Keywords
AI drug discovery; mTOR; rapalog; C. elegans; cancer; longevity
Subject
Medicine and Pharmacology, Other
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
