U 18666A Chemical Properties

Melting point:

195-196.5 °C(lit.)

storage temp. 

2-8°C

solubility 

H₂O: 9 mg/mL at ≤60 °C

form 

crystalline

color 

white

Water Solubility 

Soluble in water at 10mg/ml

Stability:

Stable for 2 years from date of purchase as supplied. Solutions in DMSO or distilled water may be stored at -20°C for up to 1 week.

InChI

1S/C25H41NO2.ClH/c1-5-26(6-2)15-16-28-19-9-7-18-8-10-20-21-11-12-23(27)24(21,3)14-13-22(20)25(18,4)17-19;/h8,19-22H,5-7,9-17H2,1-4H3;1H

InChIKey

ICPRVJHNLABCSA-UHFFFAOYSA-N

SMILES

[Cl-].N(CCOC1CC2(C3C(C4C(CC3)(C(=O)CC4)C)CC=C2CC1)C)(CC)CC.[H+]

Safety Information

Safety Statements 

22-24/25

WGK Germany 

3

Storage Class

11 - Combustible Solids

MSDS

• Language:English Provider:SigmaAldrich

U 18666A Usage And Synthesis

Description

U-18666A (3039-71-2) is an oxidosqualene reductase inhibitor.1 Inhibits the egress of cholesterol from late endosomes and lysosomes.2 U-18666A is also used to study Niemann-Pick disease and for assessing the importance of molecular trafficking through the lysosomal pathway in other conditions.3

Uses

U 18666A is a cell-permeable amphiphilic amino-steroid.

Definition

ChEBI: 3beta-(2-diethylaminoethoxy)androst-5-en-17-one hydrochloride is a hydrochloride obtained by reaction of 3beta-(2-diethylaminoethoxy)androst-5-en-17-one with one equivalent of hydrochloric acid. It is a cholesterol synthesis and transport inhibitor. It has a role as an EC 1.3.1.72 (Delta(24)-sterol reductase) inhibitor, a nicotinic antagonist, a sterol biosynthesis inhibitor, an antiviral agent and a Hedgehog signaling pathway inhibitor. It contains a 3beta-(2-diethylaminoethoxy)androst-5-en-17-one(1+).

General Description

A cell-permeable, amphiphilic amino-steroid that alters intracelluar membrane protein trafficking by impairing intracellular biosynthesis and transport of LDL-derived cholesterol. Reported to exert its effects via the inhibition of 2,3-oxidosqualene-lanosterol cyclase activity. Also reported to inhibit the activity of Δ⁸-sterol isomerase.

Biological Activity

Inhibitor of cholesterol synthesis and cellular transport, and weak inhibitor of hedgehog (Hh) signaling. Reduces serum sterol levels in rats in vivo .

Biochem/physiol Actions

Cell permeable: yes

storage

Desiccate at RT

Background

U-18666A is a cell permeable drug that inhibits cholesterol transport. This small molecule inhibits low density lipoprotein-derived cholesterol transport, blocking cholesterol esterification, and suppressing LDL receptor activities. Studies have shown that impaired cholesterol trafficking is associated with neurological diseases such as Alzheimer’s disease, Niemann-Pick disease type C, and atherosclerosis. The mechanisms of neurodegeneration for these diseases are mostly unknown so studies using U-18666A to simulate intracellular cholesterol accumulation may provide greater insight into these pathologies. Cholesterol levels play a role in the body’s response to viral infection and the ability of a virus to enter and replicate within a host cell, making U-18666A an important compound when studying different viral diseases.

References

[1] RUSSELL C. SEXTON. 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[J]. Biochemistry Biochemistry, 1983, 22 25: 5687-5692. DOI:10.1021/bi00294a001
[2] L LISCUM  J R F. 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.[J]. The Journal of Biological Chemistry, 1989, 264 20: 11796-11806.
[3] CENEDELLA R J. Cholesterol Synthesis Inhibitor U18666A and the Role of Sterol Metabolism and Trafficking in Numerous Pathophysiological Processes[J]. Lipids, 2009, 44 6: 477-487. DOI:10.1007/s11745-009-3305-7

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