Fig. 3. The results of preliminary high throughput screening and hit validation. (a) Flowchart of AlphaScreen-based high throughput screening for the discovery of hGCN5 inhibitors. (b) Inhibitory activities of top 30 compounds from high throughput screening determined by radioisotope acetylation assays. (c) The chemical structure of DC_HG24-01. (d) The IC50 determination of DC_HG24-01 against hGCN5 HAT domain measured by radioisotope acetylation assays. (e) SPR binding data for the interactions of DC_HG24-01 with hGCN5. The compound was prepared at the concentrations of 40 μM, 28.6 μM, 20.4 μM, 14.6 μM, 10.4 μM, 7.4 μM, 5.3 μM, 3.8 μM and 1.9 μM, respectively. Data in panels (d and e) is presented as mean ± SD, n = 3.
