کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10592131 | 981777 | 2014 | 4 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Discovery of BRD4 bromodomain inhibitors by fragment-based high-throughput docking
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Discovery of BRD4 bromodomain inhibitors by fragment-based high-throughput docking Discovery of BRD4 bromodomain inhibitors by fragment-based high-throughput docking](/preview/png/10592131.png)
چکیده انگلیسی
Bromodomains (BRDs) recognize acetyl-lysine modified histone tails mediating epigenetic processes. BRD4, a protein containing two bromodomains, has emerged as an attractive therapeutic target for several types of cancer as well as inflammatory diseases. Using a fragment-based in silico screening approach, we identified two small molecules that bind to the first bromodomain of BRD4 with low-micromolar affinity and favorable ligand efficiency (0.37Â kcal/mol per non-hydrogen atom), selectively over other families of bromodomains. Notably, the hit rate of the fragment-based in silico approach is about 10% as only 24 putative inhibitors, from an initial library of about 9 million molecules, were tested in vitro.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 24, Issue 11, 1 June 2014, Pages 2493-2496
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 24, Issue 11, 1 June 2014, Pages 2493-2496
نویسندگان
Hongtao Zhao, Lisa Gartenmann, Jing Dong, Dimitrios Spiliotopoulos, Amedeo Caflisch,