4FJY

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

Summary for 4FJY

• Entry DOI: 10.2210/pdb4fjy/pdb
• Related: 4FJZ 4FLH
• Descriptor: 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)
• Functional Keywords: inflammation, cancer, p110, c2 domain, leukocytes, kinase, p85, phosphotransferase, transferase-inhibitor complex, transferase/inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P48736
• Total number of polymer chains: 1
• Total formula weight: 110580.81

Authors

Whittington, D.A.,Tang, J.,Yakowec, P. (deposition date: 2012-06-12, release date: 2012-10-24, Last modification date: 2024-02-28)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.9 Å)