Fig. 2: HTS identification of HDAC and BET inhibitors that increase sCLU levels in vitro. | npj Drug Discovery

Fig. 2: HTS identification of HDAC and BET inhibitors that increase sCLU levels in vitro.

From: Discovery of a small molecule secreted clusterin enhancer that improves memory in Alzheimer’s disease mice

Fig. 2

A Scattergraph of sCLU levels from HTS of a subset of UCLA compound library at a concentration of 5 µM in U-87 MG glioblastoma cells. The UCLA module name is listed at right. B Three of 32 HTS hits significantly increase sCLU levels in U-87 MG cells in re-testing (n = 3 per compound). C Schematic showing the molecular relationship between HDAC inhibitor, vorinostat, and BET inhibitor, I-BET151in transcriptional regulation. D sCLU and nCLU levels following treatment U-87 MG cells with HDAC inhibitors vorinostat and belinostat or BET inhibitors I-BET151 and (+)-JQ1 at 5 µM (n = 6 for sCLU and n = 3 for nCLU). Dashed line at 1 represents DMSO control. E Dose-response curves showing sCLU levels and calculated EC50 values for vorinostat, belinostat, I-BET151, and (+)-JQ1 (n = 6). F Dose-response cytotoxicity testing in U-87MG cells following treatment with vorinostat, belinostat, I-BET151, and (+)-JQ1 (n = 4). All results graphed as mean ± SEM. All statistics were performed using one-way ANOVA (*p ≤ 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001). Illustrations created with Biorender.com.

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