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Interaction of DP-TAT-59, an active metabolite of new triphenylethylene-derivative (TAT-59), with estrogen receptors.

Abstract
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.
AuthorsT Toko, K Matsuo, J Shibata, K Wierzba, M Nukatsuka, S Takeda, Y Yamada, T Asao, T Hirose, B Sato
JournalThe Journal of steroid biochemistry and molecular biology (J Steroid Biochem Mol Biol) Vol. 43 Issue 6 Pg. 507-14 (Nov 1992) ISSN: 0960-0760 [Print] England
PMID1419885 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Estrogen Antagonists
  • Receptors, Estrogen
  • Tamoxifen
  • TAT 59
  • 2-(4-(1-(4-hydroxyphenyl)-2-(4-isopropylphenyl)-1-butenyl)phenoxy)-N,N-dimethylethylamine
  • Estradiol
  • Chloramphenicol O-Acetyltransferase
Topics
  • Animals
  • Binding, Competitive
  • Cell Division (drug effects)
  • Chloramphenicol O-Acetyltransferase (biosynthesis)
  • Estradiol (metabolism)
  • Estrogen Antagonists (metabolism, pharmacology)
  • Female
  • Leydig Cells (metabolism)
  • Male
  • Rats
  • Receptors, Estrogen (isolation & purification, metabolism)
  • Tamoxifen (analogs & derivatives, metabolism, pharmacology)
  • Testicular Neoplasms (metabolism)
  • Transcription, Genetic
  • Transfection
  • Tumor Cells, Cultured
  • Uterus (metabolism)

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