Pharmacological activities of droloxifene isomers

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.