4E73

Crystal structure of JNK1beta-JIP in complex with an azaquinolone inhbitor

4E73 の概要

• エントリーDOI: 10.2210/pdb4e73/pdb
• 関連するPDBエントリー: 1UKH
• 分子名称: Mitogen-activated protein kinase 8, C-Jun-amino-terminal kinase-interacting protein 1, methyl 3-(4-{[(1R,2S,3S,5S,7s)-5-aminotricyclo[3.3.1.1~3,7~]dec-2-yl]carbamoyl}benzyl)-4-oxo-1-phenyl-1,4-dihydro-1,8-naphthyridine-2-carboxylate, ... (4 entities in total)
• 機能のキーワード: kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm: P45983; Cytoplasm (By similarity): Q9UQF2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 44468.45

構造登録者

Lukacs, C.M.,Janson, C.A. (登録日: 2012-03-16, 公開日: 2013-05-29, 最終更新日: 2023-09-13)

主引用文献

Haynes, N.E.,Scott, N.R.,Chen, L.C.,Janson, C.A.,Li, J.K.,Lukacs, C.M.,Railkar, A.,Tozzo, E.,Whittard, T.,Brown, N.F.,Cheung, A.W.
Identification of an Adamantyl Azaquinolone JNK Selective Inhibitor.
ACS Med Chem Lett, 3:764-768, 2012

PubMed Abstract: 3-[4-((1S,2S,3R,5S,7S)-5-Hydroxyadamantan-2-ylcarbamoyl)benzyl]-4-oxo-1-phenyl-1,4-dihydro-[1,8]naphthyridine-2-carboxylic acid methyl ester (4) was identified as a novel, druglike and selective quinolone pan JNK inhibitor. In this communication, some of the structure-activity relationship of the azaquinolone analogues leading to 4 is discussed. The focus is on how changes at the amide functionality affected the biochemical potency, cellular potency, metabolic properties, and solubility of this class of JNK inhibitors. Optimization of these properties led to the identification of the adamantyl analogue, 4. 4 achieved proof of mechanism in both rat and mouse TNF-α challenge models.

PubMed: 24900545
DOI: 10.1021/ml300175c

実験手法

X-RAY DIFFRACTION (2.27 Å)