targetmol bioactive compound library  (TargetMol)

Journal: Alzheimer's Research & Therapy

Article Title: Proof-of-concept study: APOE4 brain endothelial cells as a phenotypic compound screen

doi: 10.1186/s13195-026-01960-6

Figure Lengend Snippet: Compound treatment phase, mTOR inhibitors disrupt baseline TEER of APOE4 -brain endothelial cells. APOE4 -brain endothelial cells were treated for 24 h with 1 µM of 900 + compounds selected from the TargetMol Bioactive Library. A Capacitance was > 4nF for 11 compounds, 4 of which inhibit cell cycle pathways (CDK, purple dots) and 3 PI3K/Akt/mTOR (blue dots). B , C Relative change and percentage activity of compounds. We identified compounds that either increased (light green dots, 5 compounds) or decreased (brown dots, 34 compounds) baseline TEER. 22 were inhibitors of mTOR/PI3K (blue dots) including rapamycin (arrow). E - I The ability of mTOR activators (NV-5138, L-leucine, 3BDO, MHY1485) to modulate LPS-induced TEER disruption was evaluated. E , G Compound treatment phase. E. High concentrations of mTOR activators were either toxic (2 mM L-leucine; 200 µM 3BDO) or F. disrupted TEER (100 µM 3BDO). H , I LPS Phase. High concentrations of NV-5138 (10 µM) mitigated LPS-induced TEER disruption. Data analyzed by one-Way ANOVA/matched Mixed-effects model (REML) followed by Dunnet’s multiple comparisons test comparing a compound concentration to the control group. In the compound treatment phase ( F ), * p < 0.05 for a given compound concentration compared to vehicle. In the LPS treatment phase ( H ), * p < 0.05 for a given compound concentration + LPS compared to the vehicle plus LPS group. n = 3. Upper lines indicate the concentrations different from LPS control for each compound. All statistical analysis is provided in Additional File 2

Article Snippet: We then screened a subset of ~ 900 molecules from the TargetMol Bioactive Library and identified two main groups compounds.

Techniques: Activity Assay, Disruption, Concentration Assay, Control, Analysis