9I13

Human protein kinase CK2 alpha in complex with TN19

これはPDB形式変換不可エントリーです。

9I13 の概要

• エントリーDOI: 10.2210/pdb9i13/pdb
• 関連するPDBエントリー: 8C6M 8C6N 9I0Z 9I10 9I11 9I12
• 分子名称: Casein kinase II subunit alpha, SULFATE ION, (2~{Z},5~{Z})-2-(3-fluorophenyl)imino-5-[(4-methoxy-3-oxidanyl-phenyl)methylidene]-1,3-thiazolidin-4-one, ... (5 entities in total)
• 機能のキーワード: kinase domain, 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: 39998.44

構造登録者

Dalle Vedove, A.,Cazzanelli, G.,Lolli, G. (登録日: 2025-01-15, 公開日: 2025-02-26, 最終更新日: 2026-02-18)

主引用文献

Cazzanelli, G.,Dalle Vedove, A.,Broso, F.,Burigotto, M.,Zasso, J.,Aiello, G.,Zonta, F.,Astolfi, A.,Barreca, M.L.,Ruzzene, M.,Tiberi, L.,Fava, L.L.,Quattrone, A.,Lolli, G.
Switching off CK2-mediated activation of survivin offers new therapeutic opportunities in neuroblastoma.
Exp.Mol.Med., 58:227-242, 2026

PubMed Abstract: CK2 is an antiapoptotic kinase overactive in various malignancies. Here we show that CK2 inhibition dramatically affects neuroblastoma growth both in vitro and in vivo. In particular, here we report on the identification of CK2-TN03, a CK2 inhibitor showing greater selectivity and cellular efficacy than silmitasertib, the only available clinical grade CK2 inhibitor with orphan status for cholangiocarcinoma and in clinical trials for medulloblastoma. CK2-TN03 acts by suppressing survivin, which is overexpressed in all high-risk neuroblastomas. Survivin function is affected by direct inhibition of its phosphorylation by CK2; its messenger RNA and protein levels are reduced through CK2 regulation of the MDM2/p53 balance via AKT1 and BRD4/MYCN. Accordingly, neuroblastoma cells persistently stall in mitosis before going to apoptosis. Finally, CK2-TN03 does not affect noncycling cells and significantly reduces tumor growth in mice xenografts without any apparent toxicity.

PubMed: 41571889
DOI: 10.1038/s12276-025-01628-5

実験手法

X-RAY DIFFRACTION (1.75 Å)