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.
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005260:Female; D006801:Humans; D007700:Kinetics; D010647:Phenyl Ethers / Q000494:pharmacology*; D011955:Receptors, Drug; D011960:Receptors, Estrogen / Q000378:metabolism*; D013629:Tamoxifen / Q000378:metabolism* / Q000494:pharmacology
D010647:Phenyl Ethers; D011955:Receptors, Drug; D011960:Receptors, Estrogen; D013629:Tamoxifen; C043062:tesmilifene