4FJY

Crystal structure of PI3K-gamma in complex with quinoline-indoline inhibitor 24f

4FJY の概要

• エントリーDOI: 10.2210/pdb4fjy/pdb
• 関連するPDBエントリー: 4FJZ 4FLH
• 分子名称: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform, SULFATE ION, 4-[3,3-dimethyl-6-(morpholin-4-yl)-2,3-dihydro-1H-indol-1-yl]-7-fluoro-3-methyl-2-(pyridin-3-yl)quinoline, ... (4 entities in total)
• 機能のキーワード: inflammation, cancer, p110, c2 domain, leukocytes, kinase, p85, phosphotransferase, transferase-inhibitor complex, 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: 110580.81

構造登録者

Whittington, D.A.,Tang, J.,Yakowec, P. (登録日: 2012-06-12, 公開日: 2012-10-24, 最終更新日: 2024-02-28)

主引用文献

Gonzalez-Lopez de Turiso, F.,Shin, Y.,Brown, M.,Cardozo, M.,Chen, Y.,Fong, D.,Hao, X.,He, X.,Henne, K.,Hu, Y.L.,Johnson, M.G.,Kohn, T.,Lohman, J.,McBride, H.J.,McGee, L.R.,Medina, J.C.,Metz, D.,Miner, K.,Mohn, D.,Pattaropong, V.,Seganish, J.,Simard, J.L.,Wannberg, S.,Whittington, D.A.,Yu, G.,Cushing, T.D.
Discovery and in Vivo Evaluation of Dual PI3K-beta/delta inhibitors
J.Med.Chem., 55:7667-7685, 2012

PubMed Abstract: Structure-based rational design led to the synthesis of a novel series of potent PI3K inhibitors. The optimized pyrrolopyridine analogue 63 was a potent and selective PI3Kβ/δ dual inhibitor that displayed suitable physicochemical properties and pharmacokinetic profile for animal studies. Analogue 63 was found to be efficacious in animal models of inflammation including a keyhole limpet hemocyanin (KLH) study and a collagen-induced arthritis (CIA) disease model of rheumatoid arthritis. These studies highlight the potential therapeutic value of inhibiting both the PI3Kβ and δ isoforms in the treatment of a number of inflammatory diseases.

PubMed: 22876881
DOI: 10.1021/jm300679u

実験手法

X-RAY DIFFRACTION (2.9 Å)