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
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موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله

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 (IC50Â =Â 8Â nM) and good cellular activity (EC50Â =Â 310Â 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
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 22, Issue 1, 1 January 2012, Pages 65-70
نویسندگان
Xianhai Huang, Xiaohong Zhu, Xiao Chen, Wei Zhou, Dong Xiao, Sylvia Degrado, Robert Aslanian, James Fossetta, Daniel Lundell, Fang Tian, Prashant Trivedi, Anandan Palani,