9GCW
Crystal structure of protein kinase CK2 catalytic subunit (csnk2a1 gene product) in complex with the dual CK2/HDAC inhibitor IOR-160
This is a non-PDB format compatible entry.
Summary for 9GCW
| Entry DOI | 10.2210/pdb9gcw/pdb |
| Descriptor | Casein kinase II subunit alpha, 5-[[8-(oxidanylamino)-8-oxidanylidene-octyl]amino]benzo[c][2,6]naphthyridine-8-carboxylic acid, CHLORIDE ION, ... (4 entities in total) |
| Functional Keywords | protein kinase ck2, casein kinase 2, dual ck2/hdac inhibitor, transferase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 42152.77 |
| Authors | |
| Primary citation | Ortin, I.,Ochoa-Callejero, L.,Werner, C.,Lindenblatt, D.,Niefind, K.,Martinez, A.,de Pascual-Teresa, B.,Ramos, A. Targeting Casein Kinase 2 and Histone Deacetylase with a Dual Inhibitor Effectively Reduces Tumor Growth in a Triple-Negative Breast Cancer Xenograft Model. Acs Pharmacol Transl Sci, 8:2093-2105, 2025 Cited by PubMed Abstract: In a previous study, was identified as a potent dual inhibitor of CK2 and HDAC enzymes. In this study, we evaluated its selectivity and therapeutic potential. exhibited high selectivity for CK2 within a panel of 21 kinases and more widespread inhibitory activity against histone deacetylases (HDAC 1, 2, 3, and 6, low activity for HDAC8). Using a mouse model of triple-negative breast cancer (MDA-MB-231), we further explored its effects on disease progression. Notably, animals treated with exhibited no detectable signs of toxicity or behavioral side effects relative to untreated mice. In a xenograft study, significantly reduced tumor growth ( = 0.0336) and decreased tumor burden ( = 0.0454) compared to the vehicle (DMSO)-treated group. In addition, modulated critical cellular signaling pathways, demonstrated by the inhibition of AKT phosphorylation ( = 0.0175) and a significant increase in acetylated α-tubulin ( = 0.0023), confirming the dual action of . Furthermore, X-ray crystallography revealed the binding mode of to CK2, showing high conservation compared to that of the known CK2 inhibitor CX-4945. These results suggest that has significant potential as an antitumor agent. Nonclinical and clinical studies become now necessary to validate the efficacy of this new chemical entity as a potential drug. PubMed: 40672667DOI: 10.1021/acsptsci.5c00192 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.86 Å) |
Structure validation
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