Fig. 1

i-BET858 exhibits increased efficacy compared to other BETi in cell lines and primary samples. A Protein lysates from ovarian cancer cell lines were subjected to western blot analyses to study basal BET protein expression (BRD2, BRD3, BRD4). GAPDH was used as loading control. B, C and D Determination of IC₅₀ values (µM) using 2D (B) and 3D (C) models of ovarian cancer cell lines. Cells were treated for 48 h with varying concentrations of i-BET858, i-BET151 and i-BET726 (10 pM–10 µM). DMSO was used as vehicle control, and staurosporine was used as positive control (+). (E) Microscopy images of 3D spheroids of SKOV3 and OVCAR-3 cells treated with varying concentrations of i-BET151 and i-BET858 (10 nM–10 µM) and vehicle control. Scales represent 100 µm. (F) Protein lysates from patient derived primary cells were subjected to western blot analyses to study basal protein expression of BRD2, BRD3 and BRD4. GAPDH was used as loading control. (G) Determination of IC₅₀ values (µM) using 2D models of HGSC primary cells treated for 48 h with varying concentrations of i-BET858, i-BET151 and i-BET726 (10 pM–10 µM)