کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1358898 981371 2015 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Current kinase inhibitors cover a tiny fraction of fragment space
ترجمه فارسی عنوان
مهار کننده های فعلی کیناز یک قطعه کوچک از فضای قطعه را پوشش می دهند
کلمات کلیدی
کیناز، فضای شیمیایی، کشف مواد مخدر مبتنی بر قطعه، تقسیم بندی، سیستم حلقه های سه حلقه ای
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
چکیده انگلیسی

We analyze the chemical space coverage of kinase inhibitors in the public domain from a fragment point of view. A set of 26,668 kinase inhibitors from the ChEMBL database of bioactive molecules were decomposed automatically by fragmentation at rotatable bonds. Remarkably, about half of the resulting 10,302 fragments originate from inaccessible libraries, as they are not present in commercially available compounds. By mapping to the established kinase pharmacophore models, privileged fragments in sub-pockets are identified, for example, the 5681 ring-containing fragments capable of forming bi-dentate hydrogen bonds with the hinge region in the ATP binding site. Surprisingly, hinge-binding fragments in current kinase inhibitors cover only 1% of the potential hinge-binders obtained by decomposing a library of nearly 7.5 million commercially available compounds, which indicates that a large fraction of chemical space is unexplored.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 25, Issue 11, 1 June 2015, Pages 2372–2376
نویسندگان
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