کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10593076 981804 2012 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A three-step protocol for lead optimization: Quick identification of key conformational features and functional groups in the SAR studies of non-ATP competitive MK2 (MAPKAPK2) inhibitors
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
A three-step protocol for lead optimization: Quick identification of key conformational features and functional groups in the SAR studies of non-ATP competitive MK2 (MAPKAPK2) inhibitors
چکیده انگلیسی
A three-step protocol for SAR development was introduced and applied to the SAR studies of the MK2 inhibitor program. Following this protocol, key conformational features and functional groups for improving MK2 inhibitor activity were quickly identified. Through this effort, the initial gap observed between in vitro binding activity and cellular activity in the lead identification stage was very much reduced. Compound 28 was identified with single digit binding activity (IC50 = 8 nM) and good cellular activity (EC50 = 310 nM). This provides further evidence that non-ATP-competitive binding MK2 inhibitors are feasible by targeting the outside ATP pocket.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 22, Issue 1, 1 January 2012, Pages 65-70
نویسندگان
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