4IDV

Crystal Structure of NIK with compound 4-{3-[2-amino-5-(2-methoxyethoxy)pyrimidin-4-yl]-1H-indol-5-yl}-2-methylbut-3-yn-2-ol (13V)

4IDV の概要

• エントリーDOI: 10.2210/pdb4idv/pdb
• 関連するPDBエントリー: 4IDT
• 分子名称: Mitogen-activated protein kinase kinase kinase 14, 4-{3-[2-amino-5-(2-methoxyethoxy)pyrimidin-4-yl]-1H-indol-5-yl}-2-methylbut-3-yn-2-ol (3 entities in total)
• 機能のキーワード: nik, nuclear factor (nf)-kb, p100 processing, 2-aminopyrimidine, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: Q99558
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 158048.47

構造登録者

Liu, J.,Sudom, A.,Wang, Z. (登録日: 2012-12-13, 公開日: 2013-04-17, 最終更新日: 2024-02-28)

主引用文献

Li, K.,McGee, L.R.,Fisher, B.,Sudom, A.,Liu, J.,Rubenstein, S.M.,Anwer, M.K.,Cushing, T.D.,Shin, Y.,Ayres, M.,Lee, F.,Eksterowicz, J.,Faulder, P.,Waszkowycz, B.,Plotnikova, O.,Farrelly, E.,Xiao, S.H.,Chen, G.,Wang, Z.
Inhibiting NF-KB-inducing kinase (NIK): Discovery, structure-based design, synthesis, structure activity relationship, and co-crystal structures
Bioorg.Med.Chem.Lett., 23:1238-1244, 2013

PubMed Abstract: The discovery, structure-based design, synthesis, and optimization of NIK inhibitors are described. Our work began with an HTS hit, imidazopyridinyl pyrimidinamine 1. We utilized homology modeling and conformational analysis to optimize the indole scaffold leading to the discovery of novel and potent conformationally constrained inhibitors such as compounds 25 and 28. Compounds 25 and 31 were co-crystallized with NIK kinase domain to provide structural insights.

PubMed: 23374866
DOI: 10.1016/j.bmcl.2013.01.012

実験手法

X-RAY DIFFRACTION (2.9 Å)