A diphenylmethane derivative selective for the anti-estrogen binding site may help define its biological role.

By employing as a probe the new compound, N,N-diethyl-2-[(4-phenyl-methyl)-phenoxy]-ethanamine X HC1 (N,N-DPPE), which preferentially binds the anti-estrogen binding site, it is demonstrated that this site appears to contribute to the growth inhibitory action of tamoxifen on MCF-7 human breast cancer cells, even at lower concentrations of this anti-estrogen (1 X 10(-7) M to 1 X 10(-6) M) at which the major effect is clearly mediated via estrogen receptor. The combination of N,N-DPPE and tamoxifen is additive and this effect is not abolished by 17 beta-estradiol. This suggests that the anti-estrogen binding site is not simply a passive reservoir for binding tamoxifen, but may itself mediate the cytotoxic effects of specific ligands.