AI-Predicted mTOR Inhibitor Reduces Cancer Cell Proliferation and Extends the Lifespan of C. elegans
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 to be capable of slowing aging. We used machine learning to predict novel small molecules ta...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI
2023
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| Subjects: | |
| Online Access: | View Fulltext in Publisher View in Scopus |
| LEADER | 01813nam a2200265Ia 4500 | ||
|---|---|---|---|
| 001 | 10.3390-ijms24097850 | ||
| 008 | 230529s2023 CNT 000 0 und d | ||
| 020 | |a 16616596 (ISSN) | ||
| 245 | 1 | 0 | |a AI-Predicted mTOR Inhibitor Reduces Cancer Cell Proliferation and Extends the Lifespan of C. elegans |
| 260 | 0 | |b MDPI |c 2023 | |
| 856 | |z View Fulltext in Publisher |u https://doi.org/10.3390/ijms24097850 | ||
| 856 | |z View in Scopus |u https://www.scopus.com/inward/record.uri?eid=2-s2.0-85159258256&doi=10.3390%2fijms24097850&partnerID=40&md5=eb35262ff87a70710cd4a0c10a051f1e | ||
| 520 | 3 | |a 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 to be capable of slowing 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 modeled TKA001 binding in silico by molecular docking and molecular dynamics. TKA001 potently inhibits both TOR complex 1 and 2 signaling in vitro. Furthermore, TKA001 inhibits human cancer cell proliferation in vitro and extends the lifespan of Caenorhabditis elegans, suggesting that TKA001 is able to slow aging in vivo. © 2023 by the authors. | |
| 650 | 0 | 4 | |a AI drug discovery |
| 650 | 0 | 4 | |a C. elegans |
| 650 | 0 | 4 | |a cancer |
| 650 | 0 | 4 | |a longevity |
| 650 | 0 | 4 | |a mTOR |
| 650 | 0 | 4 | |a rapalog |
| 700 | 1 | 0 | |a Dakhovnik, A. |e author |
| 700 | 1 | 0 | |a Ewald, C.Y. |e author |
| 700 | 1 | 0 | |a Hrabovskyi, O. |e author |
| 700 | 1 | 0 | |a MacArthur, M.R. |e author |
| 700 | 1 | 0 | |a Vidovic, T. |e author |
| 773 | |t International Journal of Molecular Sciences | ||