کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1998910 | 1065827 | 2007 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A specific and potent inhibitor of glucosylceramide synthase for substrate inhibition therapy of Gaucher disease
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: A specific and potent inhibitor of glucosylceramide synthase for substrate inhibition therapy of Gaucher disease A specific and potent inhibitor of glucosylceramide synthase for substrate inhibition therapy of Gaucher disease](/preview/png/1998910.png)
چکیده انگلیسی
An approach to treating Gaucher disease is substrate inhibition therapy which seeks to abate the aberrant lysosomal accumulation of glucosylceramide. We have identified a novel inhibitor of glucosylceramide synthase (Genz-112638) and assessed its activity in a murine model of Gaucher disease (D409V/null). Biochemical characterization of Genz-112638 showed good potency (IC50 â¼Â 24 nM) and specificity against the target enzyme. Mice that received drug prior to significant accumulation of substrate (10 weeks of age) showed reduced levels of glucosylceramide and number of Gaucher cells in the spleen, lung and liver when compared to age-matched control animals. Treatment of older mice that already displayed significant amounts of tissue glucosylceramide (7 months old) resulted in arrest of further accumulation of the substrate and appearance of additional Gaucher cells in affected organs. These data indicate that substrate inhibition therapy with Genz-112638 represents a viable alternate approach to enzyme therapy to treat the visceral pathology in Gaucher disease.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Genetics and Metabolism - Volume 91, Issue 3, July 2007, Pages 259-267
Journal: Molecular Genetics and Metabolism - Volume 91, Issue 3, July 2007, Pages 259-267
نویسندگان
Kerry Anne McEachern, John Fung, Svetlana Komarnitsky, Craig S. Siegel, Wei-Lien Chuang, Elizabeth Hutto, James A. Shayman, Gregory A. Grabowski, Johannes M.F.G. Aerts, Seng H. Cheng, Diane P. Copeland, John Marshall,