7A4B

Crystal structure of human protein kinase CK2alpha (CSNK2A1 gene product) in complex with the ATP-competitive inhibitor 5,6-dibromo-1H-triazolo[4,5-b]pyridine

Summary for 7A4B

• Entry DOI: 10.2210/pdb7a4b/pdb
• Related: 7A1B 7A49
• Descriptor: Casein kinase II subunit alpha, GLYCEROL, 5,6-dibromo-1H-triazolo[4,5-b]pyridine, ... (5 entities in total)
• Functional Keywords: protein kinase ck2, casein kinase 2, atp-competitive inhibitor, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 81738.05

Authors

Niefind, K.,Lindenblatt, D.,Toelzer, C.,Bretner, M.,Chojnacki, K.,Wielechowska, M.,Winska, P. (deposition date: 2020-08-19, release date: 2020-12-09, Last modification date: 2024-01-31)

Primary citation

Chojnacki, K.,Lindenblatt, D.,Winska, P.,Wielechowska, M.,Toelzer, C.,Niefind, K.,Bretner, M.
Synthesis, biological properties and structural study of new halogenated azolo[4,5-b]pyridines as inhibitors of CK2 kinase.
Bioorg.Chem., 106:104502-104502, 2021

PubMed Abstract: The new halogenated 1H-triazolo[4,5-b]pyridines and 1H-imidazo[4,5-b]pyridines were synthesised as analogues of known CK2 inhibitors: 4,5,6,7-tetrabromo-1H-benzotriazole (TBBt) and 4,5,6,7-tetrabromo-1H-benzimidazole (TBBi). Their influence on the activity of recombinant human CK2α, CK2α' and PIM1 kinases was determined. The most active inhibitors were di- and trihalogenated 1H-triazolo[4,5-b]pyridines (4a, 5a and 10a) with IC values 2.56, 3.82 and 3.26 μM respectively for CK2α. Furthermore, effect on viability of cancer cell lines MCF-7 (human breast adenocarcinoma) and CCRF-CEM (T lymphoblast leukemia) of all final compounds was evaluated. Finally, three crystal structures of complexes of CK2α with inhibitors 4a, 5a and 10a were obtained. In addition, new protocol was used to obtain high-resolution crystal structures of CK2α' in complex with four inhibitors (4a, 5a, 5b, 10a).

PubMed: 33317841
DOI: 10.1016/j.bioorg.2020.104502

Experimental method

X-RAY DIFFRACTION (2.06 Å)