4FJZ
Crystal structure of PI3K-gamma in complex with pyrrolo-pyridine inhibitor 63
Summary for 4FJZ
| Entry DOI | 10.2210/pdb4fjz/pdb |
| Related | 4FJY 4FLH |
| Descriptor | Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform, SULFATE ION, 1'-[7-fluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-yl]-6'-(morpholin-4-yl)-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine], ... (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 | 110719.90 |
| 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 Cited by 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: 22876881DOI: 10.1021/jm300679u PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3 Å) |
Structure validation
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