8C5Q
CK2 kinase bound to inhibitor AB668
Summary for 8C5Q
| Entry DOI | 10.2210/pdb8c5q/pdb |
| Descriptor | Casein kinase II subunit alpha, SULFATE ION, 2-methylpropyl 5-fluoranyl-3-[1-[[1-[2-[[4-(2-methylpropyl)phenyl]sulfonylamino]ethyl]piperidin-4-yl]methyl]-1,2,3-triazol-4-yl]-1~{H}-indole-2-carboxylate, ... (6 entities in total) |
| Functional Keywords | kinase bivalent inhibitor, transferase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 88433.44 |
| Authors | Krimm, I.,Guichou, J.F. (deposition date: 2023-01-10, release date: 2024-01-24, Last modification date: 2025-02-05) |
| Primary citation | Bancet, A.,Frem, R.,Jeanneret, F.,Mularoni, A.,Bazelle, P.,Roelants, C.,Delcros, J.G.,Guichou, J.F.,Pillet, C.,Coste, I.,Renno, T.,Battail, C.,Cochet, C.,Lomberget, T.,Filhol, O.,Krimm, I. Cancer selective cell death induction by a bivalent CK2 inhibitor targeting the ATP site and the allosteric alpha D pocket. Iscience, 27:108903-108903, 2024 Cited by PubMed Abstract: Although the involvement of protein kinase CK2 in cancer is well-documented, there is a need for selective CK2 inhibitors suitable for investigating CK2 specific roles in cancer-related biological pathways and further exploring its therapeutic potential. Here, we report the discovery of AB668, an outstanding selective inhibitor that binds CK2 through a bivalent mode, interacting both at the ATP site and an allosteric αD pocket unique to CK2. Using caspase activation assay, live-cell imaging, and transcriptomic analysis, we have compared the effects of this bivalent inhibitor to representative ATP-competitive inhibitors, CX-4945, and SGC-CK2-1. Our results show that in contrast to CX-4945 or SGC-CK2-1, AB668, by targeting the CK2 αD pocket, has a distinct mechanism of action regarding its anti-cancer activity, inducing apoptotic cell death in several cancer cell lines and stimulating distinct biological pathways in renal cell carcinoma. PubMed: 38318383DOI: 10.1016/j.isci.2024.108903 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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