Löser R, Seibel K, Huber H J
Klinge Pharma GmbH, Munich, F.R.G.
Anticancer Res. 1988 Nov-Dec;8(6):1271-4.
Droloxifene (DROL) is a new antiestrogen which is used for the treatment of endocrine-responsive breast cancer in humans. As Droloxifene exists in a Z- and E-isomer, we investigated the main pharmacological properties of both isomers. For both compounds the following tests were conducted: affinity for the estrogen receptor (ER); effect on the growth of rat uteri; influence on the growth of the ER + human breast cancer cell line ZR-75; and isomer interconversion in vitro. DROL-(Z) had binding affinity to the cytosolic ER approximately ten times lower than that of DROL-(E). Furthermore, the estrogenic effect of DROL-(Z) in the rat uterus is weak and there is no antiestrogenic activity. The lack of antiestrogenic activity of DROL-(Z) in contrast to DROL-(E) could also be shown in the human breast cancer cells ZR-75. Thus DROL-(Z) is, as far as investigated, without antiestrogenic and estrogenic activities. Of note is the stability of both DROL-isomers. There is no interconversion or metabolism of the parent compounds DROL-(E) and DROL-(Z) in vitro.
屈洛昔芬（DROL）是一种新型抗雌激素药物，用于治疗人类内分泌反应性乳腺癌。由于屈洛昔芬存在Z型和E型异构体，我们研究了这两种异构体的主要药理特性。对这两种化合物进行了以下测试：对雌激素受体（ER）的亲和力；对大鼠子宫生长的影响；对ER + 人乳腺癌细胞系ZR-75生长的影响；以及体外异构体的相互转化。DROL-(Z)对胞质ER的结合亲和力比对DROL-(E)的亲和力低约10倍。此外，DROL-(Z)在大鼠子宫中的雌激素作用较弱，且没有抗雌激素活性。与DROL-(E)相比，DROL-(Z)在人乳腺癌细胞ZR-75中也缺乏抗雌激素活性。因此，就所研究的情况而言，DROL-(Z)没有抗雌激素和雌激素活性。值得注意的是两种DROL异构体的稳定性。母体化合物DROL-(E)和DROL-(Z)在体外没有相互转化或代谢。
