8C8C

Crystal Structure of Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (PI5P4Ka) bound to an inhibitor

8C8C の概要

• エントリーDOI: 10.2210/pdb8c8c/pdb
• 分子名称: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha, ~{N}-(3-chloranyl-4-methoxy-phenyl)-7-(3,4-dimethylphenyl)pyrrolo[2,3-d]pyrimidin-4-amine (3 entities in total)
• 機能のキーワード: inhibitor, atp, transferase
• 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: 43238.24

構造登録者

Harborne, S.P.D.,Howard, T.D.,Ogg, D.T. (登録日: 2023-01-19, 公開日: 2023-04-26, 最終更新日: 2024-06-19)

主引用文献

Willems, H.M.G.,Edwards, S.,Boffey, H.K.,Chawner, S.J.,Green, C.,Romero, T.,Winpenny, D.,Skidmore, J.,Clarke, J.H.,Andrews, S.P.
Identification of ARUK2002821 as an isoform-selective PI5P4K alpha inhibitor.
Rsc Med Chem, 14:934-946, 2023

PubMed Abstract: The phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) play a central role in regulating cell signalling pathways and, as such, have become therapeutic targets for diseases such as cancer, neurodegeneration and immunological disorders. Many of the PI5P4Kα inhibitors that have been reported to date have suffered from poor selectivity and/or potency and the availability of better tool molecules would facilitate biological exploration. Herein we report a novel PI5P4Kα inhibitor chemotype that was identified through virtual screening. The series was optimised to deliver ARUK2002821 (36), a potent PI5P4Kα inhibitor (pIC = 8.0) which is selective other PI5P4K isoforms and has broad selectivity against lipid and protein kinases. ADMET and target engagement data are provided for this tool molecule and others in the series, as well as an X-ray structure of 36 solved in complex with its PI5P4Kα target.

PubMed: 37252102
DOI: 10.1039/d3md00039g

実験手法

X-RAY DIFFRACTION (2.096 Å)