Fig. 2
OP-1074 is a pure antiestrogen and antagonizes uterotrophic activity. a Pure antiestrogens do not stimulate alkaline phosphatase (AP) activity in vitro. Ishikawa cells were treated with compounds for 3 days in the absence of E2 (agonist mode) and assayed for AP activity. Values were normalized for activity of 500 pM E2 in a representative experiment, ±s.e.m., from triplicate wells. b Antagonism of E2-stimulated AP activity. Ishikawa cells were similarly treated with compounds as above but in the presence of 500 pM E2 and assayed for AP activity. c Only the 3R-position of the methylpyrrolidine group lacks AP activity in the agonist mode. Shown is a representative figure analyzed and presented as above. Note that compounds tested here were mixtures of approximately equal amounts of active and inactive diastereomers. d Uterine wet weight measured at the end of 3 days after orally treating ovariectomized BALB/c mice daily with vehicle or 50 mg/kg tamoxifen, 100 mg/ml OP-1074 (mixture of active and inactive diastereomers), or subcutaneously with 50 mg/kg fulvestrant. Half the animals in each group were also administered 0.1 μg/ml E2 subcutaneously. Bars represent mean uterine wet weight ± s.e.m., n = 5 animals. *denotes statistical significant from vehicle; **denotes statistical significance from E2 control (p < 0.05, one-way ANOVA)
