4N9C

Fragment-based Design of 3-Aminopyridine-derived Amides as Potent Inhibitors of Human Nicotinamide Phosphoribosyltransferase (NAMPT)

4N9C の概要

• エントリーDOI: 10.2210/pdb4n9c/pdb
• 関連するPDBエントリー: 4N9B 4N9D 4N9E
• 分子名称: Nicotinamide phosphoribosyltransferase, 5-nitro-1H-benzimidazole, PHOSPHATE ION, ... (4 entities in total)
• 機能のキーワード: transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: P43490
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 114400.96

構造登録者

Dragovich, P.S.,Zhao, G.,Baumeister, T.,Bravo, B.,Giannetti, A.M.,Ho, Y.,Hua, R.,Li, G.,Liang, X.,O'Brien, T.,Skelton, N.J.,Wang, C.,Zhao, Q.,Oh, A.,Wang, W.,Wang, Y.,Xiao, Y.,Yuen, P.,Zak, M.,Zheng, X. (登録日: 2013-10-20, 公開日: 2014-02-19, 最終更新日: 2024-02-28)

主引用文献

Dragovich, P.S.,Zhao, G.,Baumeister, T.,Bravo, B.,Giannetti, A.M.,Ho, Y.C.,Hua, R.,Li, G.,Liang, X.,Ma, X.,O'Brien, T.,Oh, A.,Skelton, N.J.,Wang, C.,Wang, W.,Wang, Y.,Xiao, Y.,Yuen, P.W.,Zak, M.,Zhao, Q.,Zheng, X.
Fragment-based design of 3-aminopyridine-derived amides as potent inhibitors of human nicotinamide phosphoribosyltransferase (NAMPT).
Bioorg.Med.Chem.Lett., 24:954-962, 2014

PubMed Abstract: 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 (IC50=19 and 15 nM, respectively) as well as robust antiproliferative properties in A2780 cell culture experiments (IC50=121 and 99 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.

PubMed: 24433859
DOI: 10.1016/j.bmcl.2013.12.062

実験手法

X-RAY DIFFRACTION (1.751 Å)