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
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
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
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: Q15392 Gene ID: 1718.0 Gene Symbol: DHCR24 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/467524 |
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Target ID: CHEMBL1907596 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19183258 |
8.0 nM [IC50] | ||
Target ID: map04340 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10926779 |
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Target ID: GO:0030301 |
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Target ID: map04210 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16797161 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
Nonisotopic method for estimating cholesterogenesis in the rat. | 1976 |
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Induction of chronic epileptiform activity in the rat by an inhibitor of cholesterol synthesis, U18666A. | 1978 Jul 14 |
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Mechanism of cataract production by 3-beta(2-diethylaminoethoxy) androst-5-en-17-one hydrochloride, U18666A: an inhibitor of cholesterol biosynthesis. | 1979 Jun |
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Concentration-dependent effects of AY-9944 and U18666A on sterol synthesis in brain. Variable sensitivities of metabolic steps. | 1980 Oct 15 |
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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 |
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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 |
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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 |
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Lysosomal accumulation of unesterified cholesterol in model macrophage foam cells. | 1993 May 5 |
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Localization of Niemann-Pick C1 protein in astrocytes: implications for neuronal degeneration in Niemann- Pick type C disease. | 1999 Feb 16 |
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U18666A inhibits intracellular cholesterol transport and neurotransmitter release in human neuroblastoma cells. | 1999 Jan |
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Cyclopamine inhibition of Sonic hedgehog signal transduction is not mediated through effects on cholesterol transport. | 2000 Aug 15 |
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Binding between the Niemann-Pick C1 protein and a photoactivatable cholesterol analog requires a functional sterol-sensing domain. | 2004 Aug 24 |
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Cholesterol synthesis inhibitor U18666A and the role of sterol metabolism and trafficking in numerous pathophysiological processes. | 2009 Jun |
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U18666A, a cholesterol-inhibition agent, modulates human neuronal nicotinic acetylcholine receptors heterologously expressed in SH-EP1 cell line. | 2009 Mar |
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Effects of cholesterol transport inhibitor U18666A on APP metabolism in rat primary astrocytes. | 2017 Nov |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=7084137 https://www.ncbi.nlm.nih.gov/pubmed/678974
Curator's Comment: in rats
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23250759
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
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Edited
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Record UNII |
539DN9NA2P
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Record Status |
Validated (UNII)
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Record Version |
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