کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1368959 981737 2015 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
High throughput screening identifies ATP-competitive inhibitors of the NLRP1 inflammasome
کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
High throughput screening identifies ATP-competitive inhibitors of the NLRP1 inflammasome
چکیده انگلیسی

Nod-like receptors (NLRs) are cytoplasmic pattern recognition receptors that are promising targets for the development of anti-inflammatory therapeutics. Drug discovery efforts targeting NLRs have been hampered by their inherent tendency to form aggregates making protein generation and the development of screening assays very challenging. Herein we report the results of an HTS screen of NLR family member NLRP1 (NLR family, pyrin domain-containing 1) which was achieved through the large scale generation of recombinant GST-His-Thrombin-NLRP1 protein. The screen led to the identification of a diverse set of ATP competitive inhibitors with micromolar potencies. Activity of these hits was confirmed in a FP binding assay, and two homology models were employed to predict the possible binding mode of the leading series and facilitate further lead-optimization. These results highlight a promising strategy for the identification of inhibitors of NLR family members which are rapidly emerging as key drivers of inflammation in human disease.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 25, Issue 14, 15 July 2015, Pages 2739–2743
نویسندگان
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