6PYS

Human PI3Kalpha in complex with Compound 2-10 ((3S)-3-benzyl-3-methyl-5-[5-(2-methylpyrimidin-5-yl)pyrazolo[1,5-a]pyrimidin-3-yl]-1,3-dihydro-2H-indol-2-one)

6PYS の概要

• エントリーDOI: 10.2210/pdb6pys/pdb
• 分子名称: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform, (3S)-3-benzyl-3-methyl-5-[5-(2-methylpyrimidin-5-yl)pyrazolo[1,5-a]pyrimidin-3-yl]-1,3-dihydro-2H-indol-2-one, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: pi3kalpha kinase, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 110613.78

構造登録者

Lesburg, C.A.,Augustin, M.A. (登録日: 2019-07-30, 公開日: 2019-08-28, 最終更新日: 2024-03-13)

主引用文献

Fradera, X.,Methot, J.L.,Achab, A.,Christopher, M.,Altman, M.D.,Zhou, H.,McGowan, M.A.,Kattar, S.D.,Wilson, K.,Garcia, Y.,Augustin, M.A.,Lesburg, C.A.,Shah, S.,Goldenblatt, P.,Katz, J.D.
Design of selective PI3K delta inhibitors using an iterative scaffold-hopping workflow.
Bioorg.Med.Chem.Lett., 29:2575-2580, 2019

PubMed Abstract: PI3Kδ mediates key immune cell signaling pathways and is a target of interest for multiple indications in immunology and oncology. Here we report a structure-based scaffold-hopping strategy for the design of chemically diverse PI3Kδ inhibitors. Using this strategy, we identified several scaffolds that can be combined to generate new PI3Kδ inhibitors with high potency and isoform selectivity. In particular, an oxindole-based scaffold was found to impart exquisite selectivity when combined with several hinge binding motifs.

PubMed: 31416665
DOI: 10.1016/j.bmcl.2019.08.004

実験手法

X-RAY DIFFRACTION (2.19 Å)