Inactivation of the uterine estrogen receptor binding of estradiol during P-450 catalyzed metabolism of chlorotrianisene (TACE). Speculation that TACE antiestrogenic activity involves covalent binding to the estrogen receptor.
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Kupfer D, Bulger WH
Inactivation of the uterine estrogen receptor binding of estradiol during P-450 catalyzed metabolism of chlorotrianisene (TACE). Speculation that TACE antiestrogenic activity involves covalent binding to the estrogen receptor.
FEBS Lett. 1990 Feb 12;261(1):59-62.
- PubMed ID
- 2307235 [ View in PubMed]
- Abstract
Chlorotrianisene (TACE) exhibits in vitro little or no binding to the uterine estrogen receptor (ER) but demonstrates potent estrogenic activity in vivo, indicating that TACE is a proestrogen/proantiestrogen. Our earlier studies demonstrated that the incubation of TACE with rat liver microsomes and NADPH generates a reactive intermediate (T*) which binds covalently to proteins. The current study examined the possibility that T* may inactivate the uterine ER. The incubation of TACE with rat liver microsomes and NADPH in the presence of rat uteri, under conditions which generate T*, markedly decreased the binding capacity of the ER for [3H]estradiol (E2). The evidence indicates that ER inactivation was probably due to irreversible (covalent) binding of T* to the E2 binding site. The possibility that the antiestrogenic action of TACE and of other triphenylethylenes involves such a novel mechanism is discussed.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Chlorotrianisene Estrogen receptor alpha Protein Humans YesAgonistDetails