Figure 8
VPC-16230 and VPC-16225 inhibit oestrogen receptor-alpha transcriptional activity in tamoxifen-resistant cells. Dose–response curves (0.1 to 50 μM) of compound VPC-16225 for transcriptional inhibition of transiently transfected oestradiol (E2)-responsive luciferase reporter in the tamoxifen-resistant (TamR) cell lines (A) TamR3 (half-maximal inhibitory concentration (IC50): 8.2 μM) and (B) TamR6 (IC50: 7.2 μM). VPC-16230 inhibits oestrogen receptor-alpha (ERα) transcriptional activity in a dose-dependent manner in (C) TamR3 cells (IC50: 4.7 μM) and (D) TamR6 cells (IC50: 4.7 μM). Dose–response curves (0.000095 to 50 μM) of fulvestrant (IC50 in TamR3: 0.09 μM; IC50 in TamR6: 0.04 μM) and tamoxifen (0.000095 to 6 μM) are shown for comparison. Data points represent average of two independent experiments performed in triplicates. Error bars indicate standard error of mean for n = 6 values. Data were fitted using GraphPad Prism 5 to calculate the log of the concentration of the inhibitors versus percentage activation.