2F7E

PKA complexed with (S)-2-(1H-Indol-3-yl)-1-(5-isoquinolin-6-yl-pyridin-3-yloxymethyl-etylamine

2F7E の概要

• エントリーDOI: 10.2210/pdb2f7e/pdb
• 関連するPDBエントリー: 1YDR
• 分子名称: cAMP-dependent protein kinase, alpha-catalytic subunit, PKI inhibitory peptide, (1S)-2-(1H-INDOL-3-YL)-1-{[(5-ISOQUINOLIN-6-YLPYRIDIN-3-YL)OXY]METHYL}ETHYLAMINE, ... (4 entities in total)
• 機能のキーワード: protein kinase a, akt inhibitors, transferase
• 由来する生物種: Bos taurus (cattle)
• 細胞内の位置: Cytoplasm: P00517
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 43298.53

構造登録者

Stoll, V.S. (登録日: 2005-11-30, 公開日: 2006-06-27, 最終更新日: 2024-02-14)

主引用文献

Li, Q.,Woods, K.W.,Thomas, S.,Zhu, G.D.,Packard, G.,Fisher, J.,Li, T.,Gong, J.,Dinges, J.,Song, X.,Abrams, J.,Luo, Y.,Johnson, E.F.,Shi, Y.,Liu, X.,Klinghofer, V.,Des Jong, R.,Oltersdorf, T.,Stoll, V.S.,Jakob, C.G.,Rosenberg, S.H.,Giranda, V.L.
Synthesis and structure-activity relationship of 3,4'-bispyridinylethylenes: discovery of a potent 3-isoquinolinylpyridine inhibitor of protein kinase B (PKB/Akt) for the treatment of cancer.
Bioorg.Med.Chem.Lett., 16:2000-2007, 2006

PubMed Abstract: Structure-based design and synthesis of the 3,4'-bispyridinylethylene series led to the discovery of 3-isoquinolinylpyridine 13a as a potent PKB/Akt inhibitor with an IC(50) of 1.3nM against Akt1. Compound 13a shows excellent selectivity against distinct families of kinases such as tyrosine kinases and CAMK, and displays poor to marginal selectivity against closely related kinases in the AGC and CMGC families. Moreover, 13a demonstrates potent cellular activity comparable to staurosporine, with IC(50) values of 0.42 and 0.59microM against MiaPaCa-2 and the Akt1 overexpressing FL5.12-Akt1, respectively. Inhibition of phosphorylation of the Akt downstream target GSK3 was also observed in FL5.12-Akt1 cells with an EC(50) of 1.5microM. The X-ray structures of 12 and 13a in complex with PKA in the ATP-binding site were determined.

PubMed: 16413780
DOI: 10.1016/j.bmcl.2005.12.065

実験手法

X-RAY DIFFRACTION (2 Å)