title: RU 58,668, a new pure antiestrogen inducing a regression of human mammary carcinoma implanted in nude mice.
abstract: RU 58,668, a new steroidal antiestrogen, has been synthesized. Its in vitro and in vivo pharmacological activities have been compared to those of tamoxifen and ICI 182,780. In vitro, it displayed affinities for human and murine estrogen receptors equivalent to those of 4-hydroxy-tamoxifen, along with moderate affinities for progestin and glucocorticoid receptors. RU 58,668 proved to be a potent antiproliferative agent on MCF-7 cells stimulated by estradiol, or by exogenous or endogenous growth factors (IC50, 0.01 nM). It also inhibited the growth of the insulin-stimulated T47D cell line. In vivo, RU 58,668 displayed a total anti-uterotrophic activity in mice or rats without exhibiting any agonistic effect. Moreover, RU 58,668 was the only antiestrogenic compound tested so far to be able to induce a long term regression of human mammary MCF-7 tumors implanted in nude mice, suggesting its potential use for the treatment of advanced breast cancer.
authors.affiliation: Centre de Recherches Roussel UCLAF, Romainville, France.
authors.forename: P
authors.initials: P
authors.lastname: Van de Velde
authors.forename: F
authors.initials: F
authors.lastname: Nique
authors.forename: F
authors.initials: F
authors.lastname: Bouchoux
authors.forename: J
authors.initials: J
authors.lastname: Brémaud
authors.forename: M C
authors.initials: MC
authors.lastname: Hameau
authors.forename: D
authors.initials: D
authors.lastname: Lucas
authors.forename: C
authors.initials: C
authors.lastname: Moratille
authors.forename: S
authors.initials: S
authors.lastname: Viet
authors.forename: D
authors.initials: D
authors.lastname: Philibert
authors.forename: G
authors.initials: G
authors.lastname: Teutsch
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents; D002455:Cell Division / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011374:Progesterone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000378:metabolism; D013950:Thymus Gland / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014599:Uterus / Q000187:drug effects; D005466:Fluorocarbons
chemical_list: D000970:Antineoplastic Agents; D004958:Estradiol; D004965:Estrogen Antagonists; D000077267:Fulvestrant; D011374:Progesterone; D011960:Receptors, Estrogen; D013629:Tamoxifen; C086511:RU 58668; D005466:Fluorocarbons; C016601:afimoxifene