کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1370793 | 981830 | 2011 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Design strategies to target crystallographic waters applied to the Hsp90 molecular chaperone
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موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
A series of novel and potent small molecule Hsp90 inhibitors was optimized using X-ray crystal structures. These compounds bind in a deep pocket of the Hsp90 enzyme that is partially comprised by residues Asn51 and Ser52. Displacement of several water molecules observed crystallographically in this pocket using rule-based strategies led to significant improvements in inhibitor potency. An optimized inhibitor (compound 17) exhibited potent Hsp90 inhibition in ITC, biochemical, and cell-based assays (Kd = 1.3 nM, Ki = 15 nM, and cellular IC50 = 0.5 μM).
A series of pyrrolopyrimines as Hsp90 inhibitor was discovered from a HTS hit using structure based design strategies.Figure optionsDownload as PowerPoint slide
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 21, Issue 12, 15 June 2011, Pages 3557–3562
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 21, Issue 12, 15 June 2011, Pages 3557–3562
نویسندگان
Pei-Pei Kung, Piet-Jan Sinnema, Paul Richardson, Michael J. Hickey, Ketan S. Gajiwala, Fen Wang, Buwen Huang, Guy McClellan, Jeff Wang, Karen Maegley, Simon Bergqvist, Pramod P. Mehta, Robert Kania,