Tamoxifen aziridines: Effective inactivators of the estrogen receptor

Two analogs of the antiestrogen tamoxifen, which bear a chemically reactive aziridine function in place of the dimethylamino group, bind to the estrogen receptor from rat uterus and from MCF-7 human breast cancer cells and appear to react irreversibly with the receptor at the estrogen binding site, in a time-and concentration-dependent fashion. Because these compounds are effective receptor inactivators in uterus and breast cancer cells, they should prove to be useful probes for investigating the role of receptor in regulating cellular responses to estrogen and in studying the dynamics of estrogen receptor synthesis and turnover.