9R5C

Crystal structure of human protein kinase CK2 catalytic subunit (isoenzyme ck2alpha'; CSNK2A2 gene product) in complex with 4,7-dibromo-5,6-difluoro-1H-1,2,3-benzotriazole

This is a non-PDB format compatible entry.

Summary for 9R5C

• Entry DOI: 10.2210/pdb9r5c/pdb
• Descriptor: Casein kinase II subunit alpha', 4,7-bis(bromanyl)-5,6-bis(fluoranyl)-1~{H}-benzotriazole, 3-(4,5,6,7-tetrabromo-1H-benzotriazol-1-yl)propan-1-ol, ... (4 entities in total)
• Functional Keywords: human protein kinase ck2, human casein kinase 2, isoenzyme ck2alpha', csnk2a2, 4, 7-dibromo-5, 6-difluoro-1h-1, 2, 3-benzotriazole, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 43685.55

Authors

Kasperowicz, S.,Werner, C.,Podsiadla-Bialoskorska, M.,Szolajska, E.,Lindenblatt, D.,Niefind, K.,Poznanski, J.,Winiewska-Szajewska, M. (deposition date: 2025-05-08, release date: 2026-01-14)

Primary citation

Kasperowicz, S.,Werner, C.,Podsiadla-Bialoskorska, M.,Szolajska, E.,Maciejewska, A.M.,Lindenblatt, D.,Niefind, K.,Poznanski, J.,Winiewska-Szajewska, M.
Novel fluoro-brominated benzotriazoles as potential CK2 inhibitors. How does fluorination affect the properties of benzotriazoles?
Bioorg.Chem., 169:109446-109446, 2025

PubMed Abstract: Incorporating fluorine into ligand structures is one of the most common and widely used modifications in modern drug design and pharmacology. Substitution with this small electronegative atom alters physicochemical and pharmacological properties, including standard ADME (Absorption, Distribution, Metabolism, and Excretion) parameters, thereby modulating the activity. In this analysis, we explore these effects using a well-studied model of the catalytic domain of human protein kinase CK2 (hCK2α) and halogenated derivatives of 1-H-benzotriazole (Bt). Replacing hydrogen atoms with fluorine alters ligands' inhibitory activity and physicochemical properties, making some more suitable for therapeutic applications. Among the compounds analyzed, 5,6-dibromo-4,7-difluoro-1H-benzotriazole (FBBF) was identified as a promising lead for the further development of CK2 inhibitors.

PubMed: 41461124
DOI: 10.1016/j.bioorg.2025.109446

Experimental method

X-RAY DIFFRACTION (1.04 Å)