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Estrogen receptors interaction with Estracyt and degradation products, a biochemical study on a potential agent in the treatment of breast cancer

par Leclercq, Guy ;Heuson, Jean-Claude ;Deboel, Marie Christine
Référence European journal of drug metabolism and pharmacokinetics, 1, 2, page (77-84)
Publication Publié, 1976-04

Article révisé par les pairs

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Résumé :

Estracyt is a nitrogen mustard derivative of estradiol-17-phosphate and thereby a candidate for the treatment of breast carcinoma. Binding of Estracyt to estrogen receptors of rat uterine cytosol was studied by competitive inhibition of the binding of3H-estradiol-17 β. Rapid degradation of the drug into higher binding affinity compounds precluded an accurate assessment of its binding affinity but the highest estimate yielded values 10,000 and 100 times lower than that of estradiol-17 β and U 11, 100 A, respectively. Binding of Estracyt and its degradation products was reversible and did not alter the receptors. The affinity of dephosphorylated Estracyt was apparently 2 to 3 times higher than that of Estracyt. Its stability was also higher than that of Estracyt and estradiol-17-phosphate, although limited degradation occurred. Degradation of Estracyt occurred to a limited extent in rat serum but to a very marked degree in rat liver cytoplasmic preparations. Dephosphorylated Estracyt remained stable in these preparations. These data suggest that Estracyt administration results in flooding the organism with compounds having high affinity for the estrogen receptors and resultant saturation of their binding sites. Therefore, it is unlikely that the drug might exert significant therapeutic effects in breast cancer, based on a receptor-related mechanism. Dephosphorylated Estracyt appears more promising in this regard. © 1976 Springer-Verlag.