From Wikipedia, the free encyclopedia
Chemical compound
NC 45-0095 is a
synthetic
nonsteroidal
selective estrogen receptor modulator (SERM) which was under development by
Novo Nordisk for the treatment of
postmenopausal osteoporosis but was never marketed.
[1]
[2]
[3]
[4]
[5] It is a
partial agonist of the
estrogen receptor (
IC50Tooltip half-maximal inhibitory concentration (for
binding inhibition) = 9.5 nM;
EC50Tooltip half-maximal effective concentration = 13 nM) with mixed
estrogenic and
antiestrogenic activity, and shows full estrogenic activity in
bone and
uterus (
EmaxTooltip maximal efficacy (relative to
moxestrol, in Ishikawa
endometrial cancer
cell line) = 105%).
[1]
[4] The compound is a
pyrrolo
indolizine
derivative.
[1]
[2] Its development was discontinued by 2003.
[5]
See also
References
- ^
a
b
c Jørgensen AS, Jacobsen P, Christiansen LB, Bury PS, Kanstrup A, Thorpe SM, et al. (February 2000). "Synthesis and pharmacology of a novel pyrrolo[2,1,5-cd] indolizine (NNC 45-0095), a high affinity non-steroidal agonist for the estrogen receptor". Bioorganic & Medicinal Chemistry Letters. 10 (4): 399–402.
doi:
10.1016/S0960-894X(00)00015-9.
PMID
10714509.
- ^
a
b Sharma V, Kumar V (2014). "Indolizine: a biologically active moiety". Medicinal Chemistry Research. 23 (8): 3593–3606.
doi:
10.1007/s00044-014-0940-1.
ISSN
1054-2523.
S2CID
2643469.
-
^ Wallace OB, Richardson TI, Dodge JA (2003). "Estrogen receptor modulators: relationships of ligand structure, receptor affinity and functional activity". Current Topics in Medicinal Chemistry. 3 (14): 1663–1682.
doi:
10.2174/1568026033451727.
PMID
14683521.
- ^
a
b Meegan MJ, Lloyd DG (January 2005).
"Understanding the Molecular Mechanism of Action of Estrogen Receptor Modulators. Frontiers in Medicinal Chemistry-Online". In Atta-ur-Rahman, Reitz AB (eds.). Frontiers in Medicinal Chemistry. Vol. 2. Bentham Science Publishers. pp. 183–231 (206).
ISBN
978-1-60805-205-9.
- ^
a
b
"NNC 450095". AdisInsight. Springer Nature Switzerland AG.
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ERTooltip 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)
-
Esterified estrogens
-
Estetrol
-
Estradiol
-
Estramustine
-
Estramustine phosphate
-
Estrapronicate
-
Estrazinol
-
Estriol
-
Estrofurate
-
Estrogenic substances
-
Estromustine
-
Estrone
-
Etamestrol (eptamestrol)
-
Ethinylandrostenediol
-
Ethinylestradiol
-
Ethinylestriol
-
Ethylestradiol
-
Etynodiol
-
Etynodiol diacetate
-
Hexolame
-
Hippulin
-
Hydroxyestrone diacetate
-
Lynestrenol
-
Lynestrenol phenylpropionate
-
Mestranol
-
Methylestradiol
-
Moxestrol
-
Mytatrienediol
-
Nilestriol
-
Norethisterone
-
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)
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Mixed (
SERMsTooltip Selective estrogen receptor modulators) | |
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Antagonists |
- Coregulator-binding modulators:
ERX-11
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GPERTooltip G protein-coupled estrogen receptor | Agonists | |
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Antagonists | |
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Unknown | |
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