MONOHYDROXYLATED METABOLITE OF TAMOXIFEN WITH POTENT ANTI-ESTROGENIC ACTIVITY
MONOHYDROXYLATED METABOLITE OF TAMOXIFEN WITH POTENT ANTI-ESTROGENIC ACTIVITY
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DOI：
10.1677/joe.0.0750305
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发表时间：
1977-01-01
影响因子：
4
通讯作者：
PRESTWICH, G
中科院分区：
文献类型：
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作者：
JORDAN, VC;COLLINS, MM;PRESTWICH, G
研究了他莫昔芬及其单羟基三苯氧胺和二羟基三苯氧胺代谢产物在幼鼠体内的雌激素样和抗雌激素样作用。无论口服或皮下注射，单羟基他莫昔芬作为一种抗雌激素药物都比他莫昔芬更有效。作为一种抗雌激素，二羟基他莫昔芬的活性低于他莫昔芬，但这种衍生品本身并不能诱导子宫营养反应。他莫昔芬的两种代谢物在体外都能有效地抑制[~3H]雌二醇与雌激素受体的结合。这些代谢产物可能在他莫昔芬的抗雌激素活性中起支持作用。单羟基他莫昔芬在体内和体外的有效活性表明，该化合物可能成为雌激素和抗雌激素亚细胞研究的重要工具。
The estrogenic and antiestrogenic properties of tamoxifen and its monohydroxylated (monohydroxytamoxifen) and dihydroxylated (dihydroxytamoxifen) metabolites were investigated in the immature rat. Whether administered orally or s.c., monohydroxytamoxifen was more active than tamoxifen as an antiestrogen. Dihydroxytamoxifen was less active than tamoxifen as an antiestrogen, but this derivative alone was unable to induce a uterotrophic response. Both metabolites of tamoxifen were potent inhibitors of the binding of [3H]estradiol to estrogen receptors in vitro. It is possible that the metabolites play a supportive role in the antiestrogenic activity of tamoxifen. The potent activity of monohydroxytamoxifen in vivo and in vitro suggests that this compound could be an important new tool for the subcellular investigation of estrogenic and antiestrogenic events.