Artikel: Virtual docking screening and QSAR studies to explore AKT and mTOR inhibitors acting on PI3K in cancers.
Contemporary oncology (Poznan, Poland)
2020 Band 24, Heft 1, Seite(n) 5–12
Abstract: The phosphoinositide 3-kinase (PI3K) pathway is an important regulator of cell proliferation and metabolism. PI3K activation initiates a signal transduction cascade, of which the major effectors are the kinases AKT and mTOR. Aberrant activation of the ... ...
| Abstract | The phosphoinositide 3-kinase (PI3K) pathway is an important regulator of cell proliferation and metabolism. PI3K activation initiates a signal transduction cascade, of which the major effectors are the kinases AKT and mTOR. Aberrant activation of the PI3K/AKT/mTOR pathway is frequently observed in many human malignancies and the combination of compounds simultaneously targeting different related molecules in the PI3K/AKT/mTOR pathway leads to synergistic activity. To explore the competing common ATP inhibitors PI3K/AKT and PI3K/mTOR we developed a model PI3K-SAR 2D which made it possible to predict the bioactivity of inhibitors of AKT and mTOR towards PI3K; the interaction of the best inhibitors was evaluated by docking analysis and compared to that of dactolisib and pictilisib. A PI3K-SAR model with a correlation coefficient (R2) of 0.81706 and an RMSE of 0.16029 was obtained, which was validated and evaluated by a cross-validation method, LOO. The most predicted AKT and mTOR inhibitors present respectively pIC50 activities between 9.26-9.93 and 9.59-9.87. After docking and several comparisons, inhibitors with better predictions showed better affinity and interaction with PI3K compared to pictilisib and dactolisib, so we found that 4 inhibitors of AKT and 14 mTOR inhibitors met the criteria of Lipinski and Veber and could be future drugs. |
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| Sprache | Englisch |
| Erscheinungsdatum | 2020-02-26 |
| Erscheinungsland | Poland |
| Dokumenttyp | Journal Article |
| ISSN | 1428-2526 |
| ISSN | 1428-2526 |
| DOI | 10.5114/wo.2020.93334 |
| Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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