کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1362986 981500 2010 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Optimization of N-benzyl-benzoxazol-2-ones as receptor antagonists of macrophage migration inhibitory factor (MIF)
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Optimization of N-benzyl-benzoxazol-2-ones as receptor antagonists of macrophage migration inhibitory factor (MIF)
چکیده انگلیسی

The cytokine MIF is involved in inflammation and cell proliferation via pathways initiated by its binding to the transmembrane receptor CD74. MIF also exhibits keto–enol tautomerase activity, believed to be vestigial in mammals. Starting from a 1 μM hit from virtual screening, substituted benzoxazol-2-ones have been discovered as antagonists with IC50 values as low as 7.5 nM in a tautomerase assay and 80 nM in a MIF–CD74 binding assay. Additional studies for one of the potent inhibitors demonstrated that it is not a covalent inhibitor of MIF and that it attenuates MIF-dependent ERK1/2 phosphorylation in human synovial fibroblasts.

Substituted benzoxazol-2-ones are reported as antagonists of the signaling by macrophage migration inhibitory factor (MIF). One of the potent analogues is shown to attenuate MIF-dependent ERK1/2 phosphorylation in human synovial fibroblasts.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 20, Issue 19, 1 October 2010, Pages 5811–5814
نویسندگان
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