Fig. 7
OP-1074 shrinks tumors in tamoxifen-resistant xenograft model. MCF7/HER2/neu cells were implanted into ovariectomized athymic nude mice implanted with estrogen pellets. Animals were dosed with 100 mg/kg tamoxifen delivered daily by oral gavage, or 100 mg/kg fulvestrant delivered daily subcutaneously, or 100 mg/kg OP-1074 delivered twice daily by oral gavage. a Percent change in tumor volume compared to volume at start of treatment, with each point representing the means±s.e.m., n = 10 animals per group. *Denotes OP-1074 is statistically different from fulvestrant at end of study (student’s t-test, p < 0.05). b Waterfall plot of percent final tumor volume at end of the study compared with mean volume at start of treatment, with each bar representing one animal. c Plot of pharmacokinetic data of OP-1074 measured in mouse plasma on the final dose of OP-1074 over a 24-h period. n = 10 animals at time 0, 1, and 4 h. n = 5 animals at time 0.5, 2, 8, and 24 h. d Inhibition of transcription of LBD mutant ERα by OP-1074. Y537S-ESR1 was transiently transfected into SK-BR-3 cells along with an estrogen responsive reporter gene, ERE-tk109-Luc. Luciferase activity was assayed after treating with ligands for 22 h and values were normalized to %vehicle (no E2) control. Shown are means ± s.e.m. from triplicate wells of a representative experiment
