5AE8

Crystal structure of mouse PI3 kinase delta in complex with GSK2269557

5AE8 の概要

• エントリーDOI: 10.2210/pdb5ae8/pdb
• 関連するPDBエントリー: 5AE9
• 分子名称: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform, 6-(1H-Indol-4-yl)-4-(5-{[4-(1-methylethyl)-1-piperazinyl]methyl}-1,3-oxazol-2-yl)-1H-indazole (3 entities in total)
• 機能のキーワード: transferase, pi3 kinase delta
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 108264.20

構造登録者

Down, K.D.,Amour, A.,Baldwin, I.R.,Cooper, A.W.J.,Deakin, A.M.,Felton, L.M.,Guntrip, S.B.,Hardy, C.,Harrison, Z.A.,Jones, K.L.,Jones, P.,Keeling, S.E.,Le, J.,Livia, S.,Lucas, F.,Lunniss, C.J.,Parr, N.J.,Robinson, E.,Rowland, P.,Smith, S.,Thomas, D.A.,Vitulli, G.,Washio, Y.,Hamblin, N. (登録日: 2015-08-26, 公開日: 2015-09-16, 最終更新日: 2024-06-19)

主引用文献

Down, K.,Amour, A.,Baldwin, I.R.,Cooper, A.W.J.,Deakin, A.M.,Felton, L.M.,Guntrip, S.B.,Hardy, C.,Harrison, Z.A.,Jones, K.L.,Jones, P.,Keeling, S.E.,Le, J.,Livia, S.,Lucas, F.,Lunniss, C.J.,Parr, N.J.,Robinson, E.,Rowland, P.,Smith, S.,Thomas, D.A.,Vitulli, G.,Washio, Y.,Hamblin, J.N.
Optimization of Novel Indazoles as Highly Potent and Selective Inhibitors of Phosphoinositide 3-Kinase Gamma for the Treatment of Respiratory Disease.
J.Med.Chem., 58:7381-, 2015

PubMed Abstract: Optimization of lead compound 1, through extensive use of structure-based design and a focus on PI3Kδ potency, isoform selectivity, and inhaled PK properties, led to the discovery of clinical candidates 2 (GSK2269557) and 3 (GSK2292767) for the treatment of respiratory indications via inhalation. Compounds 2 and 3 are both highly selective for PI3Kδ over the closely related isoforms and are active in a disease relevant brown Norway rat acute OVA model of Th2-driven lung inflammation.

PubMed: 26301626
DOI: 10.1021/ACS.JMEDCHEM.5B00767

実験手法

X-RAY DIFFRACTION (2.42 Å)