3L9M

Crystal structure of PKAB3 (pka triple mutant V123A, L173M, Q181K) with compound 18

3L9M の概要

• エントリーDOI: 10.2210/pdb3l9m/pdb
• 関連するPDBエントリー: 3L9L 3L9N
• 分子名称: cAMP-dependent protein kinase catalytic subunit alpha, cAMP-dependent protein kinase inhibitor alpha, (2S)-N~1~-[5-(3-methyl-1H-indazol-5-yl)-1,3,4-thiadiazol-2-yl]-3-(4-methylphenyl)propane-1,2-diamine, ... (4 entities in total)
• 機能のキーワード: pkb, inhibitor, 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 (By similarity): P17612
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 86809.02

構造登録者

Huang, X. (登録日: 2010-01-05, 公開日: 2011-01-19, 最終更新日: 2024-11-20)

主引用文献

Zeng, Q.,Allen, J.G.,Bourbeau, M.P.,Wang, X.,Yao, G.,Tadesse, S.,Rider, J.T.,Yuan, C.C.,Hong, F.T.,Lee, M.R.,Zhang, S.,Lofgren, J.A.,Freeman, D.J.,Yang, S.,Li, C.,Tominey, E.,Huang, X.,Hoffman, D.,Yamane, H.K.,Fotsch, C.,Dominguez, C.,Hungate, R.,Zhang, X.
Azole-based inhibitors of AKT/PKB for the treatment of cancer.
Bioorg.Med.Chem.Lett., 20:1559-1564, 2010

PubMed Abstract: Through a combination of screening and structure-based rational design, we have discovered a series of N(1)-(5-(heterocyclyl)-thiazol-2-yl)-3-(4-trifluoromethylphenyl)-1,2-propanediamines that were developed into potent ATP competitive inhibitors of AKT. Studies of linker strand-binding adenine isosteres identified SAR trends in potency and selectivity that were consistent with binding interactions observed in structures of the inhibitors bound to AKT1 and to the counter-screening target PKA. One compound was shown to have acceptable pharmacokinetic properties and to be a potent inhibitor of AKT signaling and of in vivo xenograft tumor growth in a preclinical model of glioblastoma.

PubMed: 20137943
DOI: 10.1016/j.bmcl.2010.01.067

実験手法

X-RAY DIFFRACTION (1.9 Å)