Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10591097 | Bioorganic & Medicinal Chemistry Letters | 2014 | 6 Pages |
Abstract
Niemann-Pick disease type C is a fatal neurodegenerative disease, and its major cause is mutations in NPC1 gene. This gene encodes NPC1 protein, a late endosomal polytopic membrane protein required for intracellular cholesterol trafficking. One prevalent mutation (I1061T) has been shown to cause a folding defect, which results in failure of endosomal localization of the protein, leading to loss-of-function phenotype. We have previously demonstrated that several oxysterols and their derivatives act as pharmacological chaperones; binding of these compounds to NPC1I1061T mutant protein corrects the localization/maturation defect of the mutant protein. Here, we disclose detailed structure-activity relationships of oxysterol derivatives as pharmacological chaperones for NPC1I1061T mutant.
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Kenji Ohgane, Fumika Karaki, Tomomi Noguchi-Yachide, Kosuke Dodo, Yuichi Hashimoto,