inhibitor of cholesterol transport and synthesis
CAS：3039-71-2
分子式：C25H41NO2.HCl
分子量：424.07
纯度：98%
存储：Store at -20°C

Background:

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).