title: Pharmacological activities of droloxifene isomers.
abstract: 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.
authors.affiliation: Klinge Pharma GmbH, Munich, F.R.G.
authors.forename: R
authors.initials: R
authors.lastname: Löser
authors.forename: K
authors.initials: K
authors.lastname: Seibel
authors.forename: H J
authors.initials: HJ
authors.lastname: Huber
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007536:Isomerism; D007700:Kinetics; D009929:Organ Size / Q000187:drug effects; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects; D011959:Receptors, Estradiol / Q000187:drug effects / Q000378:metabolism; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology; D014599:Uterus / Q000033:anatomy & histology / Q000187:drug effects
chemical_list: D004965:Estrogen Antagonists; D012334:RNA, Neoplasm; D011959:Receptors, Estradiol; D013629:Tamoxifen; C038345:droloxifene