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Chemical compound
10β,17β-Dihydroxyestra-1,4-dien-3-one
Other names DHED; Estradiol paraquinol; Estra-1,4-diene-10β,17β-diol-3-one
Routes of administration
By mouth
[1]
Drug class
Estrogen
(8S ,9S ,10S ,13S ,14S ,17S )-10,17-dihydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a ]phenanthren-3-one
CAS Number
PubChem
CID
ChemSpider
UNII
Formula C 18 H 24 O 3
Molar mass 288.387 g·mol−1 3D model (
JSmol )
C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@@H]2O)CCC4=CC(=O)C=C[C@]34O
InChI=1S/C18H24O3/c1-17-8-7-15-13(14(17)4-5-16(17)20)3-2-11-10-12(19)6-9-18(11,15)21/h6,9-10,13-16,20-21H,2-5,7-8H2,1H3/t13-,14-,15-,16-,17-,18+/m0/s1
Key:UIKDFTLKOKNUJP-UGDFAFBOSA-N
10β,17β-Dihydroxyestra-1,4-dien-3-one (DHED ), also known as estradiol paraquinol , is an
orally active ,
centrally
selective
estrogen and a
biosynthetic
prodrug of
estradiol .
[2]
[1]
[3]
[4]
Upon systemic administration, regardless of
route of administration , DHED has been found to rapidly and selectively convert into estradiol in the
brain , whereas no such conversion occurs in the rest of the body.
[2]
[1]
[3] Moreover, DHED itself possesses no estrogenic activity, requiring
transformation into estradiol for its estrogenicity.
[2]
[1]
[3] As such, the drug shows selective estrogenic effects in the brain (e.g., alleviation of
hot flashes ,
neuroprotection ) that are said to be identical to those of estradiol, whereas estrogenic effects elsewhere in the body are not observed.
[2]
[1]
[3]
DHED has been proposed as a possible novel estrogenic treatment for
neurological and
psychiatric conditions associated with
hypoestrogenism (e.g.,
menopausal hot flashes,
depression ,
cognitive decline ,
Alzheimer's disease , and
stroke ) that uniquely lacks potentially detrimental estrogenic
side effects in the periphery.
[2]
[1]
[3]
References
^
a
b
c
d
e
f Merchenthaler I, Lane M, Sabnis G, Brodie A, Nguyen V, Prokai L, Prokai-Tatrai K (2016).
"Treatment with an orally bioavailable prodrug of 17β-estradiol alleviates hot flushes without hormonal effects in the periphery" . Sci Rep . 6 : 30721.
Bibcode :
2016NatSR...630721M .
doi :
10.1038/srep30721 .
PMC
4967894 .
PMID
27477453 .
^
a
b
c
d
e Prokai L, Nguyen V, Szarka S, Garg P, Sabnis G, Bimonte-Nelson HA, McLaughlin KJ, Talboom JS, Conrad CD, Shughrue PJ, Gould TD, Brodie A, Merchenthaler I, Koulen P, Prokai-Tatrai K (2015).
"The prodrug DHED selectively delivers 17β-estradiol to the brain for treating estrogen-responsive disorders" . Sci Transl Med . 7 (297): 297ra113.
doi :
10.1126/scitranslmed.aab1290 .
PMC
4591937 .
PMID
26203081 .
^
a
b
c
d
e Tschiffely AE, Schuh RA, Prokai-Tatrai K, Prokai L, Ottinger MA (2016).
"A comparative evaluation of treatments with 17β-estradiol and its brain-selective prodrug in a double-transgenic mouse model of Alzheimer's disease" . Horm Behav . 83 : 39–44.
doi :
10.1016/j.yhbeh.2016.05.009 .
PMC
4950979 .
PMID
27210479 .
^ Cappelletti, Maurand M. (2016). Estrogens, androgens, and the hormonal modulation of female primate sexual motivation in rhesus monkeys (Thesis).
ProQuest
1835777256 .
ER Tooltip Estrogen receptor
Agonists
Steroidal:
2-Hydroxyestradiol
2-Hydroxyestrone
3-Methyl-19-methyleneandrosta-3,5-dien-17β-ol
3α-Androstanediol
3α,5α-Dihydrolevonorgestrel
3β,5α-Dihydrolevonorgestrel
3α-Hydroxytibolone
3β-Hydroxytibolone
3β-Androstanediol
4-Androstenediol
4-Androstenedione
4-Fluoroestradiol
4-Hydroxyestradiol
4-Hydroxyestrone
4-Methoxyestradiol
4-Methoxyestrone
5-Androstenediol
7-Oxo-DHEA
7α-Hydroxy-DHEA
7α-Methylestradiol
7β-Hydroxyepiandrosterone
8,9-Dehydroestradiol
8,9-Dehydroestrone
8β-VE2
10β,17β-Dihydroxyestra-1,4-dien-3-one (DHED)
11β-Chloromethylestradiol
11β-Methoxyestradiol
15α-Hydroxyestradiol
16-Ketoestradiol
16-Ketoestrone
16α-Fluoroestradiol
16α-Hydroxy-DHEA
16α-Hydroxyestrone
16α-Iodoestradiol
16α-LE2
16β-Hydroxyestrone
16β,17α-Epiestriol (16β-hydroxy-17α-estradiol)
17α-Estradiol (
alfatradiol )
17α-Dihydroequilenin
17α-Dihydroequilin
17α-Epiestriol (16α-hydroxy-17α-estradiol)
17α-Ethynyl-3α-androstanediol
17α-Ethynyl-3β-androstanediol
17β-Dihydroequilenin
17β-Dihydroequilin
17β-Methyl-17α-dihydroequilenin
Abiraterone
Abiraterone acetate
Alestramustine
Almestrone
Anabolic steroids (e.g.,
testosterone and
esters ,
methyltestosterone ,
metandienone (methandrostenolone) ,
nandrolone and
esters , many others; via estrogenic metabolites)
Atrimustine
Bolandiol
Bolandiol dipropionate
Butolame
Clomestrone
Cloxestradiol
Conjugated estriol
Conjugated estrogens
Cyclodiol
Cyclotriol
DHEA
DHEA-S
ent -Estradiol
Epiestriol (16β-epiestriol, 16β-hydroxy-17β-estradiol)
Epimestrol
Equilenin
Equilin
ERA-63 (ORG-37663)
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Estramustine
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Estrazinol
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Hippulin
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Mytatrienediol
Nilestriol
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Noretynodrel
Orestrate
Pentolame
Prodiame
Prolame
Promestriene
RU-16117
Quinestradol
Quinestrol
Tibolone
Xenoestrogens:
Anise -related (e.g.,
anethole ,
anol ,
dianethole ,
dianol ,
photoanethole )
Chalconoids (e.g.,
isoliquiritigenin ,
phloretin ,
phlorizin (phloridzin) ,
wedelolactone )
Coumestans (e.g.,
coumestrol ,
psoralidin )
Flavonoids (incl.
7,8-DHF ,
8-prenylnaringenin ,
apigenin ,
baicalein ,
baicalin ,
biochanin A ,
calycosin ,
catechin ,
daidzein ,
daidzin ,
ECG ,
EGCG ,
epicatechin ,
equol ,
formononetin ,
glabrene ,
glabridin ,
genistein ,
genistin ,
glycitein ,
kaempferol ,
liquiritigenin ,
mirificin ,
myricetin ,
naringenin ,
penduletin ,
pinocembrin ,
prunetin ,
puerarin ,
quercetin ,
tectoridin ,
tectorigenin )
Lavender oil
Lignans (e.g.,
enterodiol ,
enterolactone ,
nyasol (cis -hinokiresinol) )
Metalloestrogens (e.g.,
cadmium )
Pesticides (e.g.,
alternariol ,
dieldrin ,
endosulfan ,
fenarimol ,
HPTE ,
methiocarb ,
methoxychlor ,
triclocarban ,
triclosan )
Phytosteroids (e.g.,
digitoxin (
digitalis ),
diosgenin ,
guggulsterone )
Phytosterols (e.g.,
β-sitosterol ,
campesterol ,
stigmasterol )
Resorcylic acid lactones (e.g.,
zearalanone ,
α-zearalenol ,
β-zearalenol ,
zearalenone ,
zeranol (α-zearalanol) ,
taleranol (teranol, β-zearalanol) )
Steroid -like (e.g.,
deoxymiroestrol ,
miroestrol )
Stilbenoids (e.g.,
resveratrol ,
rhaponticin )
Synthetic xenoestrogens (e.g.,
alkylphenols ,
bisphenols (e.g.,
BPA ,
BPF ,
BPS ),
DDT ,
parabens ,
PBBs ,
PHBA ,
phthalates ,
PCBs )
Others (e.g.,
agnuside ,
rotundifuran )
Mixed (
SERMs Tooltip Selective estrogen receptor modulators ) Antagonists
Coregulator-binding modulators:
ERX-11
GPER Tooltip G protein-coupled estrogen receptor
Agonists Antagonists Unknown