9GXY

Crystal structure of protein kinase CK2 catalytic subunit (CSNK2A2 gene product) in complex with the dual CK2/HDAC inhibitor IOR-160

これはPDB形式変換不可エントリーです。

9GXY の概要

• エントリーDOI: 10.2210/pdb9gxy/pdb
• 関連するPDBエントリー: 9GCW
• 分子名称: Casein kinase II subunit alpha', 5-[[8-(oxidanylamino)-8-oxidanylidene-octyl]amino]benzo[c][2,6]naphthyridine-8-carboxylic acid (3 entities in total)
• 機能のキーワード: protein kinase ck2, casein kinase 2, dual ck2/hdac inhibitor, 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: 43276.31

構造登録者

Werner, C.,Lindenblatt, D.,Niefind, K. (登録日: 2024-10-01, 公開日: 2025-07-30)

主引用文献

Ortin, I.,Ochoa-Callejero, L.,Werner, C.,Lindenblatt, D.,Niefind, K.,Martinez, A.,de Pascual-Teresa, B.,Ramos, A.
Targeting Casein Kinase 2 and Histone Deacetylase with a Dual Inhibitor Effectively Reduces Tumor Growth in a Triple-Negative Breast Cancer Xenograft Model.
Acs Pharmacol Transl Sci, 8:2093-2105, 2025

PubMed Abstract: In a previous study, was identified as a potent dual inhibitor of CK2 and HDAC enzymes. In this study, we evaluated its selectivity and therapeutic potential. exhibited high selectivity for CK2 within a panel of 21 kinases and more widespread inhibitory activity against histone deacetylases (HDAC 1, 2, 3, and 6, low activity for HDAC8). Using a mouse model of triple-negative breast cancer (MDA-MB-231), we further explored its effects on disease progression. Notably, animals treated with exhibited no detectable signs of toxicity or behavioral side effects relative to untreated mice. In a xenograft study, significantly reduced tumor growth ( = 0.0336) and decreased tumor burden ( = 0.0454) compared to the vehicle (DMSO)-treated group. In addition, modulated critical cellular signaling pathways, demonstrated by the inhibition of AKT phosphorylation ( = 0.0175) and a significant increase in acetylated α-tubulin ( = 0.0023), confirming the dual action of . Furthermore, X-ray crystallography revealed the binding mode of to CK2, showing high conservation compared to that of the known CK2 inhibitor CX-4945. These results suggest that has significant potential as an antitumor agent. Nonclinical and clinical studies become now necessary to validate the efficacy of this new chemical entity as a potential drug.

PubMed: 40672667
DOI: 10.1021/acsptsci.5c00192

実験手法

X-RAY DIFFRACTION (1.16 Å)