Novel antioestrogens

Abstract

SynopsisRecently described 7α-alkylamide analogues of oestradiol, exemplified by ICI 164,384, have the pharmacological characteristics of pure antioestrogens. ICI 164,384 is completely free of oestrogenic activity in rodents and blocks the trophic actions of exogenous and endogenous oestradiol and of partial agonist antiooestrogens like tamoxifen. In addition, ICI 164,384 is peripherally selective, producing complete involution of the uterus without affecting LH secretion in intact female rats.In MCF-7 oestrogen-responsive, human breast cancer cells ICI 164,384 is a more potent and effective inhibitor of cell growth than tamoxifen. This difference in efficacy is reflected by a greater reduction in the proportion of cells continuing DNA synthesis in ICI 164,384-treated cultures than in tamoxifen-treated cells. This observation implies that a pure antioestrogen may provide more effective therapy of breast cancer but this will have to be demonstrated in clinical studies.