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Details

Stereochemistry ABSOLUTE
Molecular Formula C25H41NO2
Molecular Weight 387.5985
Optical Activity UNSPECIFIED
Defined Stereocenters 6 / 6
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of 3.BETA.-(2-(DIETHYLAMINO)ETHOXY)ANDROST-5-EN-17-ONE

SMILES

[H][C@@]12CCC(=O)[C@@]1(C)CC[C@@]3([H])[C@@]2([H])CC=C4C[C@H](CC[C@]34C)OCCN(CC)CC

InChI

InChIKey=DMZCCFMMPHJWQY-BKWLFHPQSA-N
InChI=1S/C25H41NO2/c1-5-26(6-2)15-16-28-19-11-13-24(3)18(17-19)7-8-20-21-9-10-23(27)25(21,4)14-12-22(20)24/h7,19-22H,5-6,8-17H2,1-4H3/t19-,20-,21-,22-,24-,25-/m0/s1

HIDE SMILES / InChI

Molecular Formula C25H41NO2
Molecular Weight 387.5985
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 6 / 6
E/Z Centers 0
Optical Activity UNSPECIFIED

3.beta-3-[2-(Diethylamino)ethoxy]androst-5-en-17-one hydrochloride or U18666A, an amphipathic cationic amine, is a cell permeable research tool drug that inhibits cholesterol synthesis and trafficking, and also a weak inhibitor of hedgehog (Hh) signaling. U18666A had been used in several models both in vivo and in vitro to mimic Niemann-Pick type C disease (NPC) and for assessing the importance of molecular trafficking through the lysosomal pathway in other conditions such as atherosclerosis, Alzheimer's disease, and prion infections. U18666A also provided animal models for such disorders as petite mal (absence) epilepsy and cataracts. U18666A inhibits the enzyme desmosterol reductase responsible for reducing the desmosterol in cholesterol biosynthesis, and also blocks LDL-(low density lipoprotein) cholesterol transport from the lysosomes into the endoplasmic reticulum thereby increasing the level of caveolina-1 located within the plasma membrane caveolae. U18666A was shown to be a potent antagonist of alpha4beta2 neuronal nicotinic acetylcholine receptors and may be useful as a tool in the functional characterization and pharmacological profiling of nAChRs.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
PubMed

PubMed

TitleDatePubMed
Nonisotopic method for estimating cholesterogenesis in the rat.
1976
Induction of chronic epileptiform activity in the rat by an inhibitor of cholesterol synthesis, U18666A.
1978 Jul 14
Mechanism of cataract production by 3-beta(2-diethylaminoethoxy) androst-5-en-17-one hydrochloride, U18666A: an inhibitor of cholesterol biosynthesis.
1979 Jun
Concentration-dependent effects of AY-9944 and U18666A on sterol synthesis in brain. Variable sensitivities of metabolic steps.
1980 Oct 15
Studies on the mechanism of the epileptiform activity induced by U18666A. II. Concentration, half-life and distribution of radiolabeled U18666A in the brain.
1982 Jun
Effects of 3 beta-[2-(diethylamino)ethoxy]androst-5-en-17-one on the synthesis of cholesterol and ubiquinone in rat intestinal epithelial cell cultures.
1983 Dec 6
The intracellular transport of low density lipoprotein-derived cholesterol is inhibited in Chinese hamster ovary cells cultured with 3-beta-[2-(diethylamino)ethoxy]androst-5-en-17-one.
1989 Jul 15
Lysosomal accumulation of unesterified cholesterol in model macrophage foam cells.
1993 May 5
Localization of Niemann-Pick C1 protein in astrocytes: implications for neuronal degeneration in Niemann- Pick type C disease.
1999 Feb 16
U18666A inhibits intracellular cholesterol transport and neurotransmitter release in human neuroblastoma cells.
1999 Jan
Cyclopamine inhibition of Sonic hedgehog signal transduction is not mediated through effects on cholesterol transport.
2000 Aug 15
Binding between the Niemann-Pick C1 protein and a photoactivatable cholesterol analog requires a functional sterol-sensing domain.
2004 Aug 24
Cholesterol synthesis inhibitor U18666A and the role of sterol metabolism and trafficking in numerous pathophysiological processes.
2009 Jun
U18666A, a cholesterol-inhibition agent, modulates human neuronal nicotinic acetylcholine receptors heterologously expressed in SH-EP1 cell line.
2009 Mar
Effects of cholesterol transport inhibitor U18666A on APP metabolism in rat primary astrocytes.
2017 Nov
Patents

Sample Use Guides

Acute 10 mg/kg dose of U18666A (3-beta(2-diethylaminoethoxy)androst-5-en-17-one hydrochloride) or chronic injection of 10 mg/kg every 4th day
Route of Administration: Other
U18666A induced neurotoxicity and cholesterol accumulation in mouse primary hippocampal neurons. After 5 days of plating, cultured neurons were treated with 0.1–50 ug/ml U18666A for 24 h or with 5 μg/ml U18666A for 6–96 h. MTT values were significantly attenuated in concentration-dependent (A) and time-dependent (B) manners in U18666A-treated cultures compared with mock-treated cultures.
Substance Class Chemical
Created
by admin
on Sat Dec 16 10:05:27 GMT 2023
Edited
by admin
on Sat Dec 16 10:05:27 GMT 2023
Record UNII
539DN9NA2P
Record Status Validated (UNII)
Record Version
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Name Type Language
3.BETA.-(2-(DIETHYLAMINO)ETHOXY)ANDROST-5-EN-17-ONE
Systematic Name English
ANDROST-5-EN-17-ONE, 3.BETA.-(2-(DIETHYLAMINO)ETHOXY)-
Systematic Name English
LS-3360
Code English
ANDROST-5-EN-17-ONE, 3-(2-(DIETHYLAMINO)ETHOXY)-, (3.BETA.)-
Systematic Name English
Code System Code Type Description
FDA UNII
539DN9NA2P
Created by admin on Sat Dec 16 10:05:27 GMT 2023 , Edited by admin on Sat Dec 16 10:05:27 GMT 2023
PRIMARY
CAS
2855-62-1
Created by admin on Sat Dec 16 10:05:27 GMT 2023 , Edited by admin on Sat Dec 16 10:05:27 GMT 2023
PRIMARY
EPA CompTox
DTXSID2048246
Created by admin on Sat Dec 16 10:05:27 GMT 2023 , Edited by admin on Sat Dec 16 10:05:27 GMT 2023
PRIMARY
PUBCHEM
9954083
Created by admin on Sat Dec 16 10:05:27 GMT 2023 , Edited by admin on Sat Dec 16 10:05:27 GMT 2023
PRIMARY
Related Record Type Details
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