No loss of estrogenic or anti-estrogenic activity after demethylation of droloxifene (3-OH-tamoxifen).
The binding affinity of 3-OH-Tamoxifen (Droloxifene or DROL) and N-demethyl-droloxifene (ND-DROL) to the cystosolic estrogen receptor of rabbit uteri was 10 times higher than that of Tamoxifen. Both compounds exhibited similar stimulation (estrogenic effect) and inhibition (anti-estrogenic effect) of uterine growth of immature female rats. 3H-Uridine incorporation into the RNA of MCF-7 and ZR-75 cells as a measure of anti-estrogenic activity was equally inhibited by concentrations of 0.05-1.0 mumol/l of both compounds. Thus, the pharmacological properties of DROL were not changed by N-demethylation.
D000818:Animals; D001667:Binding, Competitive; D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004965:Estrogen Antagonists / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006801:Humans; D008745:Methylation; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism*; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D014599:Uterus / Q000187:drug effects / Q000378:metabolism
D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D013629:Tamoxifen; C038345:droloxifene; C047288:N-demethyldroloxifene