Abstract
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 periphery to the parent steroid. This distinguishing feature of α-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 α-DHED for a safe and efficacious 17α-estradiol-based neurotherapy.
| Original language | English |
|---|---|
| Pages (from-to) | 2528-2533 |
| Number of pages | 6 |
| Journal | ACS Chemical Neuroscience |
| Volume | 9 |
| Issue number | 11 |
| DOIs | |
| State | Published - 21 Nov 2018 |
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Keywords
- 10β,17α-dihydroxyestra-1,4-dien-3-one
- 17α-Estradiol
- ERs binding
- LC-MS/MS
- Porsolt swim test
- brain-selective bioprecursor prodrug
- ovariectomized mice
- uterotrophic effect
- α-DHED
Cite this
}
10β,17α-Dihydroxyestra-1,4-dien-3-one : A Bioprecursor Prodrug Preferentially Producing 17α-Estradiol in the Brain for Targeted Neurotherapy. / Prokai-Tatrai, Katalin; Nguyen, Vien; Prokai, Laszlo.
In: ACS Chemical Neuroscience, Vol. 9, No. 11, 21.11.2018, p. 2528-2533.Research output: Contribution to journal › Article
TY - JOUR
T1 - 10β,17α-Dihydroxyestra-1,4-dien-3-one
T2 - A Bioprecursor Prodrug Preferentially Producing 17α-Estradiol in the Brain for Targeted Neurotherapy
AU - Prokai-Tatrai, Katalin
AU - Nguyen, Vien
AU - Prokai, Laszlo
PY - 2018/11/21
Y1 - 2018/11/21
N2 - 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 periphery to the parent steroid. This distinguishing feature of α-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 α-DHED for a safe and efficacious 17α-estradiol-based neurotherapy.
AB - 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 periphery to the parent steroid. This distinguishing feature of α-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 α-DHED for a safe and efficacious 17α-estradiol-based neurotherapy.
KW - 10β,17α-dihydroxyestra-1,4-dien-3-one
KW - 17α-Estradiol
KW - ERs binding
KW - LC-MS/MS
KW - Porsolt swim test
KW - brain-selective bioprecursor prodrug
KW - ovariectomized mice
KW - uterotrophic effect
KW - α-DHED
UR - http://www.scopus.com/inward/record.url?scp=85048056691&partnerID=8YFLogxK
U2 - 10.1021/acschemneuro.8b00184
DO - 10.1021/acschemneuro.8b00184
M3 - Article
C2 - 29843514
AN - SCOPUS:85048056691
VL - 9
SP - 2528
EP - 2533
JO - ACS Chemical Neuroscience
JF - ACS Chemical Neuroscience
SN - 1948-7193
IS - 11
ER -