6OCU

HUMAN PI3KDELTA IN COMPLEX WITH COMPOUND 29

6OCU の概要

• エントリーDOI: 10.2210/pdb6ocu/pdb
• 分子名称: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform, Phosphatidylinositol 3-kinase regulatory subunit alpha, 5-{(3R)-3-methyl-4-[(1R,2R)-2-methylcyclopropane-1-carbonyl]piperazin-1-yl}-3-(1-methyl-1H-pyrazol-4-yl)pyrazine-2-carbonitrile (3 entities in total)
• 機能のキーワード: pi3kdelta kinase, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 142966.46

構造登録者

Lesburg, C.A.,Augustin, M.A. (登録日: 2019-03-25, 公開日: 2019-12-11, 最終更新日: 2024-03-13)

主引用文献

Zhou, H.,McGowan, M.A.,Lipford, K.,Christopher, M.,Fradera, X.,Witter, D.,Lesburg, C.A.,Li, C.,Methot, J.L.,Lampe, J.,Achab, A.,Shaffer, L.,Goldenblatt, P.,Shah, S.,Bass, A.,Schroeder, G.,Chen, D.,Zeng, H.,Augustin, M.A.,Katz, J.D.
Discovery and optimization of heteroaryl piperazines as potent and selective PI3K delta inhibitors.
Bioorg.Med.Chem.Lett., 30:126715-126715, 2020

PubMed Abstract: A high-throughput screening (HTS) campaign identified a class of heteroaryl piperazines with excellent baseline affinity and selectivity for phosphoinositide 3-kinase δ (PI3Kδ) over closely related isoforms. Rapid evaluation and optimization of structure-activity relationships (SAR) for this class, leveraging the modular nature of this scaffold, facilitated development of this hit class into a series of potent and selective inhibitors of PI3Kδ. This effort culminated in the identification of 29, which displayed excellent potency in enzyme and cell-based assays, as well as favorable pharmacokinetic and off-target profiles.

PubMed: 31757666
DOI: 10.1016/j.bmcl.2019.126715

実験手法

X-RAY DIFFRACTION (2.77 Å)