9H96

STRUCTURE OF PROTEIN KINASE CK2 CATALYTIC SUBUNIT (ISOFORM CK2ALPHA'; CSNK2A2 GENE PRODUCT) IN COMPLEX WITH THE INDENOINDOLE-TYPE INHIBITOR MC11

This is a non-PDB format compatible entry.

Summary for 9H96

• Entry DOI: 10.2210/pdb9h96/pdb
• Descriptor: Casein kinase II subunit alpha', 1,2-ETHANEDIOL, 1,2,3,4-tetrakis(bromanyl)-5-propan-2-yl-7,8-dihydro-6~{H}-indeno[1,2-b]indole-9,10-dione, ... (5 entities in total)
• Functional Keywords: atp-competitive inhibitor, kinase, ck2, casein kinase ii, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 43607.76

Authors

Niefind, K.,Lindenblatt, D.,Werner, C. (deposition date: 2024-10-30, release date: 2025-08-27, Last modification date: 2026-02-11)

Primary citation

Marminon, C.,Werner, C.,Gast, A.,Herfindal, L.,Charles, J.,Lindenblatt, D.,Aichele, D.,Mularoni, A.,Doskeland, S.O.,Jose, J.,Niefind, K.,Le Borgne, M.
Exploring the biological potential of the brominated indenoindole MC11 and its interaction with protein kinase CK2.
Biol.Chem., 406:125-138, 2025

PubMed Abstract: Protein kinase CK2 is a promising therapeutic target, especially in oncology. Over the years, various inhibitors have been developed, with polyhalogenated scaffolds emerging as a particularly effective class. Halogens like bromine and chlorine enhance inhibitor stability by forming additional interactions within the ATP pocket. Among halogenated scaffolds, benzotriazole and benzimidazole have led to potent molecules such as 4,5,6,7-tetrabromo-1-benzotriazole (IC = 300 nM) and 4,5,6,7-tetrabromo-2-(dimethylamino)benzimidazole (IC = 140 nM). Modifications, including 4,5,6-tribromo-7-ethyl-1-benzotriazole (IC = 160 nM), further improved activity. Changing scaffolds while retaining halogens has enabled design of new inhibitors. Flavonols, dibenzofuranones, and the indeno[1,2-]indole scaffold are key examples. Halogenation of the reference molecule 5-isopropyl-5,6,7,8-tetrahydroindeno[1,2-]indole-9,10-dione (, IC = 360 nM) significantly boosted potency. The study focused on introducing four halogens, yielding to the compound 1,2,3,4-tetrabromo-5-isopropyl-5,6,7,8-tetrahydroindeno[1,2-]indole-9,10-dione (), with an IC of 16 nM. Co-crystallography revealed how bromine atoms enhance binding, and demonstrated strong activity, particularly against leukemic cell lines like IPC-Bcl2.

PubMed: 40116007
DOI: 10.1515/hsz-2024-0160

Experimental method

X-RAY DIFFRACTION (1.04 Å)