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U 18666A

Catalog No.
B6812
inhibitor of cholesterol transport and synthesis
Grouped product items
SizePriceStock Qty
10mg
$100.00
Ship with 5-10 days
25mg
$237.00
Ship with 5-10 days
50mg
$422.00
Ship with 5-10 days

Tel: +1-832-696-8203

Email: [email protected]

Worldwide Distributors

Background

U 18666A is an inhibitor of cholesterol transport and synthesis [1] [2].

Cholesterol is a sterol that biosynthesized by all animal cells and is an essential component of all animal cell membranes that is required to maintain membrane fluidity and structural integrity.

U 18666A is an inhibitor of cholesterol transport and synthesis. In rat brain, U 18666A inhibited sterols production in a concentration-dependent way [1]. In cultured Chinese hamster ovary (CHO) cells, U18666A inhibited cholesterol esterification stimulated by low density lipoprotein (LDL)-derived cholesterol and also inhibited LDL receptor activities and 3-hydroxy-3-methylglutaryl-coenzyme A reductase. U18666A caused the accumulation of LDL-derived cholesterol in the lysosomes, suggesting the inhibition of LDL-derived cholesterol transport [2]. In cultured baby hamster kidney cells and human skin fibroblasts (HSF), U18666A reversibly and rapidly inhibited acyl-CoA cholesterol acyl transferase (ACAT) activated by sphingomyelinase in a dose dependent way. In sphingomyelinase-treated HSF cells, U18666A significantly and reversibly reduced the translocation of plasma membrane cholesterol. In mouse Leydig tumor cells, U18666A inhibited steroid hormones secretion stimulated by cyclic AMP in a dose dependent way [3]. In primary cortical neurons, U18666A caused cellular injury and caspase-3 activation. U18666A also caused the accumulation of cholesterol [4].

References:
[1].  Cenedella RJ. Concentration-dependent effects of AY-9944 and U18666A on sterol synthesis in brain. Variable sensitivities of metabolic steps. Biochem Pharmacol, 1980, 29(20): 2751-2754.
[2].  Liscum L, Faust JR. 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 Biol Chem, 1989, 264(20): 11796-11806.
[3].  Härmälä AS, Pörn MI, Mattjus P, Slotte JP. Cholesterol transport from plasma membranes to intracellular membranes is inhibited by 3 beta-[2-(diethylamino)ethoxy]androst-5-en-17-one. Biochim Biophys Acta, 1994, 1211(3): 317-325.
[4].  Cheung NS, Koh CH, Bay BH, et al. Chronic exposure to U18666A induces apoptosis in cultured murine cortical neurons. Biochem Biophys Res Commun, 2004, 315(2): 408-417.

Chemical Properties

Physical AppearanceA crystalline solid
StorageStore at -20°C
M.Wt424.07
Cas No.3039-71-2
FormulaC25H41NO2·HCl
SolubilitySoluble in H2O
Chemical Name(3S,8R,9S,10R,13S,14S)-3-(2-(diethylamino)ethoxy)-10,13-dimethyl-3,4,7,8,9,10,11,12,13,14,15,16-dodecahydro-1H-cyclopenta[a]phenanthren-17(2H)-one hydrochloride
SDFDownload SDF
Canonical SMILESO=C1[[email protected]]2(C)[[email protected]@H](CC1)[[email protected]]3[[email protected]](CC2)[[email protected]](CC[[email protected]@H]4OCCN(CC)CC)(C)C(C4)=CC3.Cl
Shipping ConditionEvaluation sample solution: ship with blue ice. All other available sizes: ship with RT, or blue ice upon request.
General tipsFor obtaining a higher solubility, please warm the tube at 37°C and shake it in the ultrasonic bath for a while. Stock solution can be stored below -20°C for several months.

Protocol

Cell experiment [1]:

Cell lines

Primary cortical neurons

Preparation method

Soluble to 100 mM in sterile water. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

0.1–2.5 μg/ml, 37°C, 72 h

Applications

U18666A (2.5 μg/ml, 72 h) induced cytotoxicity in primary cortical neurons. U18666A resulted in significant loss of more than 50% of cell survival and major morphological changes characterized by cell shrinkage and membrane blebbing in cortical neuron. U18666A (0.1–2.5 μg/ml, 72 h) induced cell injury and apoptosis in primary cortical neurons.

Animal experiment [2]:

Animal models

Sprague-Dawley rats

Dosage form

Subcutaneous injection, 10 mg/kg, every fourth or seventh day

Application

Weekly injection of U 18666A (10 mg/kg, s.c.) into neonatal rats for 4 consecutive weeks caused a reduction in the seizure threshold of male rats to the convulsant flurothyl.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. Cheung N S, Koh C H V, Bay B H, et al. Chronic exposure to U18666A induces apoptosis in cultured murine cortical neurons[J]. Biochemical and biophysical research communications, 2004, 315(2): 408-417.

[2]. Bierkamper G G, Cenedella R J. Induction of chronic epileptiform activity in the rat by an inhibitor of cholesterol synthesis, U18666A[J]. Brain research, 1978, 150(2): 343-351.

Quality Control

Quality Control & MSDS

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Chemical structure

U 18666A