9TM3

Monoclinic crystal structure of protein kinase CK2 catalytic subunit CK2alpha' (CSNK2A2 gene product) in complex with the indenoindole-precursor compound JC0151

This is a non-PDB format compatible entry.

Summary for 9TM3

• Entry DOI: 10.2210/pdb9tm3/pdb
• Descriptor: Casein kinase II subunit alpha', NICOTINIC ACID, (4bS,9bS)-4b,9b-bis(oxidanyl)-5-propan-2-yl-7,8-dihydro-6H-indeno[1,2-b]indole-9,10-dione, ... (4 entities in total)
• Functional Keywords: protein kinase ck2, kinase, inhibitor, casein kinase ii, transferase
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 86319.30

Authors

Werner, C.,Charles, J.,Le Borgne, M.,Niefind, K. (deposition date: 2025-12-11, release date: 2026-08-19)

Primary citation

Guimaraes, M.M.,Werner, C.,Leroy, B.,Charles, J.,Guillon, J.,Pinaud, N.,Mularoni, A.,Jean-Baptiste, M.,Ximenes, P.,Gast, A.,Prinz, H.,Aichele, D.,Goncalves, A.G.,Marminon, C.,Bouaziz, Z.,Jose, J.,Delcros, J.G.,Niefind, K.,Le Borgne, M.
Targeting Human Protein Kinase CK2 by a Library of Indeno[1,2-b]Indoles: Contribution of Thermal Shift Assay to Pre-Screening and Co-Crystallization to Post-Screening.
Arch Pharm, 359:e70312-e70312, 2026

PubMed Abstract: Protein kinase CK2 is the subject of numerous studies in medicinal chemistry due to its involvement in the development of several diseases, primarily cancers. Its overexpression in tumor cells is related to key processes such as tumor immune evasion and cell proliferation. The scientific approach of this study aims to investigate the thermal shift assay (TSA) as a pre-screening tool and to complement it with a co-crystallization approach in post-screening. Therefore, the synthesis of seven small-molecule CK2 inhibitors derived from indeno[1,2-b]indoles was supplemented by 18 related derivatives from our in-house compound library. The 25 molecules belong to four sub-scaffolds, namely 4b,9b-dihydroxy-4b,5,6,7,8,9b-hexahydroindeno[1,2-b]indole-9,10-dione (D-0), 5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione (D-1), 9-hydroxy-5H-indeno[1,2-b]indol-10-one (D-2), and 5H-indeno[1,2-b]indole-6,9,10-trione (D-3). The most active CK2 inhibitors identified by capillary electrophoresis (CE)-based assay belong to the D-1 sub-scaffold. In the TSA, these compounds also generate significant shifts of the melting temperature (Tm) of CK2, indicating a clear correlation between the results of the CE-based assay and those of the TSA. The contribution of co-crystallization in post-screening also demonstrated the effectiveness of D-1 sub-scaffold compared with D-0 sub-scaffold.

PubMed: 42544794
DOI: 10.1002/ardp.70312

Experimental method

X-RAY DIFFRACTION (1.2 Å)