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Cancer Chemotherapy and Pharmacology

, Volume 37, Issue 1–2, pp 7–13 | Cite as

Comparative pharmacodynamic analysis of TAT-59 and tamoxifen in rats bearing DMBA-induced mammary carcinoma

  • Toshiyuki Toko
  • Jiro Shibata
  • Yoshikazu Sugimoto
  • Hidetoshi Yamaya
  • Masahiko Yoshida
  • Kazuo Ogawa
  • Eiji Matsushima
Original Article TAT-59, Pharmacodynamics, Anti-Estrogenic Activity, DMBA-Induced Mammary Tumor

Abstract

TAT-59 suppressed the growth fo DMBA-induced mammary tumors in rats earlier and more strongly than tamoxifen (TAM). After oral administration of the drugs, DP-TAT-59, one of the main metabolites of TAT-59, was found in 10- to 15-fold higher concentrations in both the tumor and blood compared to 4-OH-TAM, an active metabolite of TAM. In a 3-day antiuterotrophic test, every detected metabolite of TAT-59 showed stronger antiestrogenic activity than did TAM. In a competition assay, the affinity of the metabolites for estrogen receptors ranged from that of estradiol to that of TAM. These results suggest that the superior antiestrogenic activity of TAT-59 compared to TAM was either due to its higher penetration into tumor tissue or to the stronger antiestrogenic activity of its metabolites.

Key words

TAT-59 Pharmacodynamics Anti-estrogenic activity DMBA-induced mammary tumor 

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Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • Toshiyuki Toko
    • 1
  • Jiro Shibata
    • 1
  • Yoshikazu Sugimoto
    • 1
  • Hidetoshi Yamaya
    • 1
  • Masahiko Yoshida
    • 1
  • Kazuo Ogawa
    • 1
  • Eiji Matsushima
    • 1
  1. 1.Tokushima Research CenterTaiho Pharmaceutical Co., Ltd.TokushimaJapan

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