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10?,17?-Dihydroxyestra-1,4-dien-3-one: A Bioprecursor Prodrug Preferentially Producing 17?-Estradiol in the Brain for Targeted Neurotherapy.

ABSTRACT: Uterotrophic effect of 17?-estradiol, the C17 epimer of the main human estrogen 17?-estradiol, was shown to manifest in animal models at doses lower than those necessary for central outcome raising concerns about its potential to treat maladies of the central nervous system. We introduce here 10?,17?-dihydroxyestra-1,4-dien-3-one (?-DHED) that acts as a bioprecursor prodrug producing 17?-estradiol with remarkable selectivity to the brain and, therefore, without appreciable exposure of the periphery to the parent steroid. This distinguishing feature of ?-DHED is shown by using an estrogen-responsive mouse model with complementary LC-MS/MS measurement of drug contents in target tissues. Our data warrant further research to fully establish the potential of ?-DHED for a safe and efficacious 17?-estradiol-based neurotherapy.

SUBMITTER: Prokai-Tatrai K

PROVIDER: S-EPMC6582959 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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10β,17α-Dihydroxyestra-1,4-dien-3-one: A Bioprecursor Prodrug Preferentially Producing 17α-Estradiol in the Brain for Targeted Neurotherapy.

Prokai-Tatrai Katalin K Nguyen Vien V Prokai Laszlo L

ACS chemical neuroscience 20180605 11

Uterotrophic effect of 17α-estradiol, the C17 epimer of the main human estrogen 17β-estradiol, was shown to manifest in animal models at doses lower than those necessary for central outcome raising concerns about its potential to treat maladies of the central nervous system. We introduce here 10β,17α-dihydroxyestra-1,4-dien-3-one (α-DHED) that acts as a bioprecursor prodrug producing 17α-estradiol with remarkable selectivity to the brain and, therefore, without appreciable exposure of the periph ...[more]

PMID: 29843514

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