3UVQ

Human p38 MAP Kinase in Complex with a Dibenzosuberone Derivative

3UVQ の概要

• エントリーDOI: 10.2210/pdb3uvq/pdb
• 関連するPDBエントリー: 3QUD 3QUE 3UVP 3UVR 3UVS
• 分子名称: Mitogen-activated protein kinase 14, N-{5-[(7-{[(2R)-2,3-dihydroxypropyl]oxy}-5-oxo-10,11-dihydro-5H-dibenzo[a,d][7]annulen-2-yl)amino]-2-fluorophenyl}benzamide, octyl beta-D-glucopyranoside, ... (4 entities in total)
• 機能のキーワード: selective p38 inhibitor, sar, dibenzosuberone derivative, protein kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 42087.98

構造登録者

Mayer-Wrangowski, S.C.,Richters, A.,Gruetter, C.,Rauh, D. (登録日: 2011-11-30, 公開日: 2012-12-05, 最終更新日: 2023-11-08)

主引用文献

Fischer, S.,Wentsch, H.K.,Mayer-Wrangowski, S.C.,Zimmermann, M.,Bauer, S.M.,Storch, K.,Niess, R.,Koeberle, S.C.,Grutter, C.,Boeckler, F.M.,Rauh, D.,Laufer, S.A.
Dibenzosuberones as p38 mitogen-activated protein kinase inhibitors with low ATP competitiveness and outstanding whole blood activity.
J.Med.Chem., 56:241-253, 2013

PubMed Abstract: p38α mitogen-activated protein (MAP) kinase is a main target in drug research concerning inflammatory diseases. Nevertheless, no inhibitor of p38α MAP kinase has been introduced to the market. This might be attributed to the fact that there is no inhibitor which combines outstanding activity in biological systems and selectivity. Herein an approach to the development of such inhibitors on the basis of the highly selective molecular probe Skepinone-L is described. Introduction of a "deep pocket" moiety addressing the DFG motif led to an increased activity of the compounds. Hydrophilic moieties, addressing the solvent-exposed area adjacent to hydrophilic region II, conserved a high activity of the compounds in a whole blood assay. Combined with their outstanding selectivity and low ATP competitiveness, these inhibitors are very interesting candidates for use in biological systems and in therapy.

PubMed: 23270382
DOI: 10.1021/jm301539x

実験手法

X-RAY DIFFRACTION (2.2 Å)