کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10594884 | 981852 | 2014 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Fragment-based design of 3-aminopyridine-derived amides as potent inhibitors of human nicotinamide phosphoribosyltransferase (NAMPT)
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The fragment-based identification of two novel and potent biochemical inhibitors of the nicotinamide phosphoribosyltransferase (NAMPT) enzyme is described. These compounds (51 and 63) incorporate an amide moiety derived from 3-aminopyridine, and are thus structurally distinct from other known anti-NAMPT agents. Each exhibits potent inhibition of NAMPT biochemical activity (IC50Â =Â 19 and 15Â nM, respectively) as well as robust antiproliferative properties in A2780 cell culture experiments (IC50Â =Â 121 and 99Â nM, respectively). However, additional biological studies indicate that only inhibitor 51 exerts its A2780 cell culture effects via a NAMPT-mediated mechanism. The crystal structures of both 51 and 63 in complex with NAMPT are also independently described.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 24, Issue 3, 1 February 2014, Pages 954-962
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 24, Issue 3, 1 February 2014, Pages 954-962
نویسندگان
Peter S. Dragovich, Guiling Zhao, Timm Baumeister, Brandon Bravo, Anthony M. Giannetti, Yen-Ching Ho, Rongbao Hua, Guangkun Li, Xiaorong Liang, Xiaolei Ma, Thomas O'Brien, Angela Oh, Nicholas J. Skelton, Chengcheng Wang, Weiru Wang, Yunli Wang,