کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1365970 981577 2006 19 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Structure-based design of isoquinoline-5-sulfonamide inhibitors of protein kinase B
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Structure-based design of isoquinoline-5-sulfonamide inhibitors of protein kinase B
چکیده انگلیسی

Structure-based drug design of novel isoquinoline-5-sulfonamide inhibitors of PKB as potential antitumour agents was investigated. Constrained pyrrolidine analogues that mimicked the bound conformation of linear prototypes were identified and investigated by co-crystal structure determinations with the related protein PKA. Detailed variation in the binding modes between inhibitors with similar overall conformations was observed. Potent PKB inhibitors from this series inhibited GSK3β phosphorylation in cellular assays, consistent with inhibition of PKB kinase activity in cells.

Novel pyrrolidine-derived isoquinoline-5-sulfonamide inhibitors of PKB were designed, and investigated crystallographically and in cellular assays.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 14, Issue 4, 15 February 2006, Pages 1255–1273
نویسندگان
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