4WWO

Crystal structure of human PI3K-gamma in complex with phenylquinoline inhibitor N-{(1S)-1-[8-chloro-2-(3-fluorophenyl)quinolin-3-yl]ethyl}-9H-purin-6-amine

4WWO の概要

• エントリーDOI: 10.2210/pdb4wwo/pdb
• 関連するPDBエントリー: 4WWN 4WWP
• 分子名称: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform, SULFATE ION, N-{(1S)-1-[8-chloro-2-(3-fluorophenyl)quinolin-3-yl]ethyl}-9H-purin-6-amine, ... (4 entities in total)
• 機能のキーワード: kinase, phosphotransfer, pip2, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm : P48736
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 110570.11

構造登録者

Whittington, D.A.,Tang, J.,Yakowec, P. (登録日: 2014-11-11, 公開日: 2014-12-17, 最終更新日: 2024-02-28)

主引用文献

Cushing, T.D.,Hao, X.,Shin, Y.,Andrews, K.,Brown, M.,Cardozo, M.,Chen, Y.,Duquette, J.,Fisher, B.,Gonzalez-Lopez de Turiso, F.,He, X.,Henne, K.R.,Hu, Y.L.,Hungate, R.,Johnson, M.G.,Kelly, R.C.,Lucas, B.,McCarter, J.D.,McGee, L.R.,Medina, J.C.,San Miguel, T.,Mohn, D.,Pattaropong, V.,Pettus, L.H.,Reichelt, A.,Rzasa, R.M.,Seganish, J.,Tasker, A.S.,Wahl, R.C.,Wannberg, S.,Whittington, D.A.,Whoriskey, J.,Yu, G.,Zalameda, L.,Zhang, D.,Metz, D.P.
Discovery and in Vivo Evaluation of (S)-N-(1-(7-Fluoro-2-(pyridin-2-yl)quinolin-3-yl)ethyl)-9H-purin-6-amine (AMG319) and Related PI3K delta Inhibitors for Inflammation and Autoimmune Disease.
J.Med.Chem., 58:480-511, 2015

PubMed Abstract: The development and optimization of a series of quinolinylpurines as potent and selective PI3Kδ kinase inhibitors with excellent physicochemical properties are described. This medicinal chemistry effort led to the identification of 1 (AMG319), a compound with an IC50 of 16 nM in a human whole blood assay (HWB), excellent selectivity over a large panel of protein kinases, and a high level of in vivo efficacy as measured by two rodent disease models of inflammation.

PubMed: 25469863
DOI: 10.1021/jm501624r

実験手法

X-RAY DIFFRACTION (2.3 Å)