3S2A

Crystal structure of PI3K-gamma in complex with a quinoline inhibitor

3S2A の概要

• エントリーDOI: 10.2210/pdb3s2a/pdb
• 分子名称: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform, SULFATE ION, N-{2-chloro-5-[4-(morpholin-4-yl)quinolin-6-yl]pyridin-3-yl}-4-fluorobenzenesulfonamide, ... (4 entities in total)
• 機能のキーワード: p110-gamma, kinase, phosphotransfer, p101, p84, leukocytes, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 110611.20

構造登録者

Whittington, D.A.,Tang, J.,Yakowec, P. (登録日: 2011-05-16, 公開日: 2011-06-08, 最終更新日: 2023-09-13)

主引用文献

Nishimura, N.,Siegmund, A.,Liu, L.,Yang, K.,Bryan, M.C.,Andrews, K.L.,Bo, Y.,Booker, S.K.,Caenepeel, S.,Freeman, D.,Liao, H.,McCarter, J.,Mullady, E.L.,San Miguel, T.,Subramanian, R.,Tamayo, N.,Wang, L.,Whittington, D.A.,Zalameda, L.,Zhang, N.,Hughes, P.E.,Norman, M.H.
Phospshoinositide 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Dual Inhibitors: Discovery and Structure-Activity Relationships of a Series of Quinoline and Quinoxaline Derivatives.
J.Med.Chem., 54:4735-4751, 2011

PubMed Abstract: The phosphoinositide 3-kinase (PI3K) family catalyzes the ATP-dependent phosphorylation of the 3'-hydroxyl group of phosphatidylinositols and plays an important role in cell growth and survival. There is abundant evidence demonstrating that PI3K signaling is dysregulated in many human cancers, suggesting that therapeutics targeting the PI3K pathway may have utility for the treatment of cancer. Our efforts to identify potent, efficacious, and orally available PI3K/mammalian target of rapamycin (mTOR) dual inhibitors resulted in the discovery of a series of substituted quinolines and quinoxalines derivatives. In this report, we describe the structure-activity relationships, selectivity, and pharmacokinetic data of this series and illustrate the in vivo pharmacodynamic and efficacy data for a representative compound.

PubMed: 21612232
DOI: 10.1021/jm200386s

実験手法

X-RAY DIFFRACTION (2.55 Å)