DP-TAT-59, (Z)-2-(4-(1-(4-hydroxyphenyl)-2-(4-isopropylphenyl)-1-butenyl) phenoxy)-N, N-
dimethylethylamine, has been reported to inhibit
estrogen-stimulated growth of MCF-7 cells as well as rat uterus at lower concentrations than the hydroxymetabolite of
tamoxifen (4-OH-TAM). In the present study, the growth of mouse
Leydig cell tumor, B-1F cells were also more effectively inhibited by
DP-TAT-59 than 4-OH-TAM. Additionally, the expression of
estrogen responsive
element ligated CAT gene transfected into B-1F cells was also suppressed by
DP-TAT-59. Thus, the interaction of
DP-TAT-59 with
estrogen receptor (ER) was characterized and compared with that of 4-OH-TAM using immature rat and bovine uteri. The dissociation constant of
DP-TAT-59 to ER of immature rat uterus was 0.24 nM and was similar to that of 4-OH-TAM (Kd = 0.20 nM) and
estradiol (Kd = 0.29 nM). Using
sucrose density gradients, the sedimentation constant of
DP-TAT-59 with bovine uterus was 4.9S, which was similar to that of
estradiol (5.1S) and 4-OH-TAM (5.3S). However, the elution profile of the DP-TAT-59-ER complex from a
DEAE-Sephadex column was different for both
estradiol-and 4-OH-TAM-ER complexes. These results suggest that ER forms different complexes with
DP-TAT-59 than
estradiol or 4-OH-TAM, while the ER binding affinity of these compounds are similar to each other.