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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]

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