3S2A

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

Summary for 3S2A

• Entry DOI: 10.2210/pdb3s2a/pdb
• Descriptor: 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)
• Functional Keywords: p110-gamma, kinase, phosphotransfer, p101, p84, leukocytes, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 110611.20

Authors

Whittington, D.A.,Tang, J.,Yakowec, P. (deposition date: 2011-05-16, release date: 2011-06-08, Last modification date: 2023-09-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.55 Å)