Löser R, Seibel K, Roos W, Eppenberger U
Eur J Cancer Clin Oncol. 1985 Aug;21(8):985-90. doi: 10.1016/0277-5379(85)90119-1.
This study demonstrates in vivo and in vitro properties of the non-steroidal antiestrogens tamoxifen (TAM), 4-OH-tamoxifen (4-OH-TAM) and 3-OH-tamoxifen (K 060 E). In immature rabbit uteri 4-OH-TAM and K 060 E bound to the respective estrogen receptors with a ten-fold higher affinity than TAM. Furthermore, K 060 E exhibited less agonistic (estrogenic) but higher antagonistic (antiestrogenic) activity in the immature rat uterus than TAM and 4-OH-TAM (change of uterine weight). The ratio of agonistic vs antagonistic effect of K 060 E was distinctly lower than in TAM and 4-OH-TAM. In addition, K 060 E reduced by approximately 45% the growth of the transplantable Fisher rat mammary tumor (R 3230 AC) as compared with TAM (33%). We assume that, due to the higher antitumor activity, K 060 E (3-OH-TAM) is a better antiestrogen than TAM.
本研究展示了非甾体类抗雌激素药物他莫昔芬（TAM）、4-羟基他莫昔芬（4-OH-TAM）和3-羟基他莫昔芬（K 060 E）的体内和体外特性。在未成熟兔子宫中，4-OH-TAM和K 060 E与各自雌激素受体的结合亲和力比TAM高10倍。此外，在未成熟大鼠子宫中，K 060 E表现出比TAM和4-OH-TAM更低的激动（雌激素）活性但更高的拮抗（抗雌激素）活性（子宫重量变化）。K 060 E激动与拮抗作用的比值明显低于TAM和4-OH-TAM。另外，与TAM（33%）相比，K 060 E使可移植的Fisher大鼠乳腺肿瘤（R 3230 AC）的生长减少了约45%。我们认为，由于更高的抗肿瘤活性，K 060 E（3-羟基他莫昔芬）是比TAM更好的抗雌激素药物。
