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℃, 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 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.

Impaired trafficking of cholesterol to or from the endoplasmic reticulum (ER) has been implicated in many disease states including Neimann-Pick disease type C (NPC), Alzheimers disease and atherosclerosis. U-18666A is a cell permeable drug that inhibits cholesterol trafficking. It inhibits cholesterol transport from late endosomes/lysosomes to the endoplasmic reticulum (ER), but not cholesterol transport to the plasma membrane as demonstrated in many cell types including macrophages, primary cortical neurons and primary fibroblasts.[1],[2],[3] In macrophages, micromolar concentrations of U-18666A inhibit multiple pathways of cholesterol trafficking from late endosomes, whereas nanomolar concentrations impair cholesterol trafficking to the ER, a response similar to that found in NPC. U-18666A inhibits oxidosqualene cyclase at high (>0.5 mM) concentrations and oral doses (10 mg/kg) induces cataracts in rats.[1]

Reference:
[1]. Koh, C.H.V., and Cheung, N.S. Cellular mechanism of U18666A-mediated apoptosis in cultured murine cortical neurons: Bridging Niemann-Pick disease type C and Alzheimer’s disease. Cellular Signalling 18(11), 1844-1853 (2006).
[2]. Tabas, I. Apoptosis and plaque destabilization in atherosclerosis: The role of macrophage apoptosis induced by cholesterol. Cell Death and Differentiation 11, S12-S16 (2004).
[3]. Feng, B., Yao, P.M., Li, Y., et al. The endoplasmic reticulum is the site of cholesterol-induced cytotoxicity in macrophages. Nature Cell Biology 5(9), 781-792 (2003).