5D9K

Rsk2 N-terminal Kinase in Complex with BI-D1870

5D9K の概要

• エントリーDOI: 10.2210/pdb5d9k/pdb
• 関連するPDBエントリー: 5D9L
• 分子名称: Ribosomal protein S6 kinase alpha-3, (7R)-2-[(3,5-difluoro-4-hydroxyphenyl)amino]-5,7-dimethyl-8-(3-methylbutyl)-7,8-dihydropteridin-6(5H)-one, GLYCEROL, ... (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)
• 細胞内の位置: Nucleus : P51812
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 76928.72

構造登録者

Appleton, B.A. (登録日: 2015-08-18, 公開日: 2015-09-02, 最終更新日: 2024-03-06)

主引用文献

Jain, R.,Mathur, M.,Lan, J.,Costales, A.,Atallah, G.,Ramurthy, S.,Subramanian, S.,Setti, L.,Feucht, P.,Warne, B.,Doyle, L.,Basham, S.,Jefferson, A.B.,Lindvall, M.,Appleton, B.A.,Shafer, C.M.
Discovery of Potent and Selective RSK Inhibitors as Biological Probes.
J.Med.Chem., 58:6766-6783, 2015

PubMed Abstract: While the p90 ribosomal S6 kinase (RSK) family has been implicated in multiple tumor cell functions, the full understanding of this kinase family has been restricted by the lack of highly selective inhibitors. A bis-phenol pyrazole was identified from high-throughput screening as an inhibitor of the N-terminal kinase of RSK2. Structure-based drug design using crystallography, conformational analysis, and scaffold morphing resulted in highly optimized difluorophenol pyridine inhibitors of the RSK kinase family as demonstrated cellularly by the inhibition of YB1 phosphorylation. These compounds provide for the first time in vitro tools with an improved selectivity and potency profile to examine the importance of RSK signaling in cancer cells and to fully evaluate RSK as a therapeutic target.

PubMed: 26270416
DOI: 10.1021/acs.jmedchem.5b00450

実験手法

X-RAY DIFFRACTION (2.55 Å)