کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1993296 1541253 2015 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
In silico identification of natural product inhibitors of JAK2
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
In silico identification of natural product inhibitors of JAK2
چکیده انگلیسی


• High-throughput virtual screening was applied to a natural product database.
• Emodic acid and 6-chloroemodic acid were identified as inhibitors of JAK2.
• The compounds inhibited JAK2 activity in vitro and in cellulo.
• The inhibition of STAT3 DNA-binding activity in nuclear extracts was demonstrated.

Emodic acid (1) and 6-chloroemodic acid (2) have been identified from a natural product database as useful scaffolds for the future development of novel JAK2 inhibitors using structure-based high-throughput virtual screening. Low-energy binding conformations of 1 and 2 in the JAK2 PTK domain were generated by virtual ligand docking and were found to overlap considerably with the binding pose of CMP6, a known JAK2 inhibitor. Compounds 1 and 2 displayed low micromolar efficacies against JAK2 enzyme activity and JAK2 autophosphorylation in human erythroleukemia cells, and inhibited STAT3 DNA-binding activity in a human hepatocarcinoma cell line.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Methods - Volume 71, 1 January 2015, Pages 21–25
نویسندگان
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