Comparative pharmacodynamic analysis of TAT-59 and tamoxifen in rats bearing DMBA-induced mammary carcinoma.
TAT-59 suppressed the growth of DMBA-induced mammary tumors in rats earlier and more strongly than tamoxifen (TAM). After oral administration of the drugs, DP-TAT-59, one of the main metabolites of TAT-59, was found in 10- to 15-fold higher concentrations in both the tumor and blood compared to 4-OH-TAM, an active metabolite of TAM. In a 3-day antiuterotrophic test, every detected metabolite of TAT-59 showed stronger antiestrogenic activity than did TAM. In a competition assay, the affinity of the metabolites for estrogen receptors ranged from that of estradiol to that of TAM. These results suggest that the superior antiestrogenic activity of TAT-59 compared to TAM was either due to its higher penetration into tumor tissue or to the stronger antiestrogenic activity of its metabolites.
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000493:pharmacokinetics*; D001667:Binding, Competitive; D004958:Estradiol / Q000378:metabolism; D004965:Estrogen Antagonists / Q000493:pharmacokinetics*; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000737:chemistry / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000032:analysis; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000627:therapeutic use
D018931:Antineoplastic Agents, Hormonal; D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D013629:Tamoxifen; C064635:TAT 59; D004958:Estradiol; D015127:9,10-Dimethyl-1,2-benzanthracene