4WWN

Crystal structure of human PI3K-gamma in complex with (S)-N-(1-(7-fluoro-2-(pyridin-2-yl)quinolin-3-yl)ethyl)-9H-purin-6-amine AMG319 inhibitor

Summary for 4WWN

• Entry DOI: 10.2210/pdb4wwn/pdb
• Related: 4WWO 4WWP
• Descriptor: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform, SULFATE ION, N-{(1S)-1-[7-fluoro-2-(pyridin-2-yl)quinolin-3-yl]ethyl}-9H-purin-6-amine, ... (4 entities in total)
• Functional Keywords: kinase, phosphotransfer, pip2, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm : P48736
• Total number of polymer chains: 1
• Total formula weight: 110344.52

Authors

Whittington, D.A.,Tang, J.,Yakowec, P. (deposition date: 2014-11-11, release date: 2014-12-17, Last modification date: 2024-02-28)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.7 Å)