7I8A

Crystal Structure of 54f bound to CK2a

これはPDB形式変換不可エントリーです。

7I8A の概要

• エントリーDOI: 10.2210/pdb7i8a/pdb
• Group deposition: the group title you wish to show (G_1002301)
• 分子名称: Casein kinase II subunit alpha, 5-({2-[4-({[3-fluoro-4-(trifluoromethoxy)phenyl]methyl}amino)butoxy]ethyl}amino)benzo[c][2,6]naphthyridine-8-carboxamide, ACETATE ION, ... (4 entities in total)
• 機能のキーワード: fragment based drug discovery, kinase, hydrolase
• 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: 39635.96

構造登録者

Brear, P.,Glossop, P.,Pandey, S.,Hyvonen, M.,Spring, D.,Butt, R.,Cawkill, D. (登録日: 2025-03-12, 公開日: 2026-01-14, 最終更新日: 2026-05-27)

主引用文献

Glossop, P.A.,Brear, P.,Wright, S.,Flanagan, N.,Glossop, M.S.,Lane, C.A.L.,Butt, R.P.,Spring, D.R.,Hyvonen, M.,Cawkill, D.
Exploiting the Cryptic alpha D Pocket of Casein Kinase 2 alpha (CK2 alpha ) to Deliver Highly Potent and Selective Type 1 Inhibitors.
J.Med.Chem., 68:21587-21614, 2025

PubMed Abstract: Casein kinase 2α (CK2α) is an oncology drug target that acts as a positive regulator of many tumorigenic signaling pathways. We previously reported that CK2α has a unique cryptic binding site, the αD pocket, that offers the potential for inhibitors with improved kinase selectivity. The prototype bivalent molecule CAM4066 () confirmed that improved selectivity could be achieved while binding in both the ATP-binding site and the αD pocket. A drug discovery project to develop a new series of bivalent CK2α inhibitors with increased cell potency and selectivity identified (APL-5125), a highly potent, ATP-competitive CK2α inhibitor with exquisite kinase selectivity and cellular potency. Compound demonstrates inhibition of p-AKT S129 in tumors (HCT116) following once-daily oral administration and shows a clear PK-PD relationship with unbound drug exposure. has a superior preclinical profile to existing CK2α inhibitors and is currently under evaluation in patients with advanced solid tumors.

PubMed: 41085029
DOI: 10.1021/acs.jmedchem.5c01807

実験手法

X-RAY DIFFRACTION (1.84 Å)