Discovery of a Novel 2,6-Disubstituted Glucosamine Series of Potent and Selective Hexokinase 2 Inhibitors [electronic resource]

• Ngôn ngữ: eng
• Ký hiệu phân loại: 547.2 Organic chemical reactions formerly 547.139
• Thông tin xuất bản: Washington, D.C. : Oak Ridge, Tenn. : United States. Dept. of Energy. Office of Science ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2015
• Mô tả vật lý: Size: p. 217-222 : , digital, PDF file.
• Bộ sưu tập: Metadata
• ID: 261081
• Chủ đề: 1. 37 inorganic, organic, physical, and analytical chemistry; 2. 60 applied life sciences; 3. Amides; 4. Carbohydrates; 5. Crystal structure; 6. Hexokinase 2 inhibitor; 7. Inhibition; 8. Inhibitors; 9. Peptides and proteins; 10. Structure?activity relationship selectivity

Tóm tắt

 A novel series of potent and selective hexokinase 2 (HK2) inhibitors, 2,6-disubstituted glucosamines, has been identified based on HTS hits, exemplified by compound 1. Inhibitor-bound crystal structures revealed that the HK2 enzyme could adopt an ?induced-fit? conformation. The SAR study led to the identification of potent HK2 inhibitors, such as compound 34 with greater than 100-fold selectivity over HK1. Compound 25 inhibits in situ glycolysis in a UM-UC-3 bladder tumor cell line via <
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