Mode of action of LN 1643 (a triphenylbromoethylene antiestrogen): probable mediation by the estrogen receptor and high affinity metabolite.

After in vivo administration of [3H]LN 1643, a triphenylbromoethylene antiestrogen, to immature female rats, polar metabolites were selectively accumulated in uterine nuclear fractions which contained most of the estrogen receptor. One metabolite comigrated with the 4-hydroxylated derivative (LN 2839) of LN 1643. LN 1643 and LN 2839 inhibited competitively and reversibly the binding of estradiol to the estrogen receptor, and the affinity of LN 2839 for the estrogen receptor was about 150-fold higher than that of LN 1643. Both compounds prevented the growth of the MCF7 human breast cancer cells and LN 2839 was about 10-fold more efficient than LN 1643. These results and previous data obtained with tamoxifen (a parent triphenylethylene antiestrogen) and its 4-hydroxylated metabolite, suggest that the antiestrogenic action of LN 1643 is mediated by the estrogen receptor as for the other synthetic antiestrogens, and that LN 1643 acts at least partly via its 4-hydroxy metabolite.