RU-58-668, A NEW PURE ANTIESTROGEN INDUCING A REGRESSION OF HUMAN MAMMARY-CARCINOMA IMPLANTED IN NUDE-MICE

RU 58 668, a new steroidal antiestrogen, has been synthesized. Its in vitro and in vivo pharmacological activities have been compared to tho se 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 glucocorti coid receptors. RU 58 668 proved to be a potent antiproliferative agen t on MCF-7 cells stimulated by estradiol, or by exogenous or endogenou s 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 tota l antiuterotrophic activity in mice or rats without exhibiting any ago nistic effect. Moreover, RU 58 668 was the only antiestrogenic compoun d tested so far to be able to induce a long term regression of human m ammary MCF-7 tumors implanted in nude mice, suggesting its potential u se for the treatment of advanced breast cancer.