کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1940882 1050790 2006 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
In vitro and in vivo characterization of a novel CCR3 antagonist, YM-344031
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
In vitro and in vivo characterization of a novel CCR3 antagonist, YM-344031
چکیده انگلیسی

Eosinophils play a prominent proinflammatory role in a broad range of diseases, including atopic dermatitis and asthma. Eotaxin-1 and its receptor CCR3 are implicated in the recruitment of eosinophils from blood into inflammatory tissues, therefore inhibition of Eotaxin-1/CCR3 interaction may have therapeutic potential for allergic inflammation with eosinophil infiltration. YM-344031, a novel and selective small molecule CCR3 antagonist, potently inhibited ligand binding (IC50 = 3.0 nM), ligand-induced Ca2+ flux (IC50 = 5.4 nM), and the chemotaxis of human CCR3-expressing cells (IC50 = 19.9 nM). YM-344031 (1–10 mg/kg) orally administered to cynomolgus monkeys significantly inhibited Eotaxin-1-induced eosinophil shape change in whole blood. Additionally, orally administered YM-344031 (100 mg/kg) prevented both immediate- and late-phase allergic skin reactions in a mouse allergy model. YM-344031 therefore has potential as a novel and orally available compound for the treatment of allergic inflammation, such as atopic dermatitis and asthma.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 339, Issue 4, 27 January 2006, Pages 1217–1223
نویسندگان
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