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Journal: iScience
Article Title: Repurposing drugs for treating the neurobehavioral manifestations of PTEN hamartoma tumor syndrome
doi: 10.1016/j.isci.2026.115428
Figure Lengend Snippet: Compound screening in SH-SY5Y PTEN −/− cells (A) Schematic of the PI3K/Akt/mTOR signaling cascade. PTEN counterbalances PI3K activity and loss of PTEN function leads to increased phosphorylation of AKT and downstream activity of mTOR. (B) Using a CRIPSR-based approach, we generated a PTEN −/− SH-SY5Y cell line. Compared to the control SH-SY5Y cells, the newly generated line shows loss of PTEN and concomitant increase of pAKT (Ser473). Loading control, GAPDH. (C–E) Highlighted are three example experiments, using different compounds. The different readouts are labeled in dark (pAKT (Ser473)) and light blue (pS6 (Ser240/244)). (C) Buparlisib similarly reduced both targets with low micromolar IC50. (D) Sapanisertib is effective at even lower concentrations. (E) SCH772984 only modestly decreases pS6 at high concentrations; however, increases pAKT levels. In all three graphs, LDH curves (orange and red) indicate the general viability. None of the displayed compounds shows sign of toxicity, even though LDH levels rise ∼15% in (C). n = 6 for each compound (2 independent experiments with 3 replicates each). Shown are mean and SEM.
Article Snippet: Knockout of
Techniques: Activity Assay, Phospho-proteomics, Generated, Control, Labeling