Summary for 9HKP
| Entry DOI | 10.2210/pdb9hkp/pdb |
| Descriptor | Casein kinase II subunit alpha, [1-[2-[[4-(2-methylpropyl)phenyl]sulfonylamino]ethyl]piperidin-4-yl]methyl 1~{H}-indole-3-carboxylate, SULFATE ION, ... (4 entities in total) |
| Functional Keywords | protein kinase ck2 fragment ligand, transferase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 87939.45 |
| Authors | |
| Primary citation | Grenier, D.,Gelin, M.,Yang, Y.,Mularoni, A.,Guichou, J.F.,Delcros, J.G.,Krimm, I. Binding-Site Switch for Protein Kinase CK2 Inhibitors. Chemmedchem, 20:e202400868-e202400868, 2025 Cited by PubMed Abstract: The serine/threonine protein kinase CK2, a tetramer composed of a regulatory dimer (CK2β) bound to two catalytic subunits CK2α, is a well-established therapeutic target for various pathologies, including cancer and viral infections. Several types of CK2 inhibitors have been developed, including inhibitors that bind to the catalytic ATP-site, bivalent inhibitors that occupy both the CK2α ATP-site and the αD pocket, and inhibitors that target the CK2α/CK2β interface. Interestingly, the bivalent inhibitor AB668 shares a similar chemical structure with the interface inhibitor CCH507. In this study, we designed analogs of CCH507 using structure-based and fragment-based approaches. The ability of these analogs to bind the CK2α/CK2β interface was evaluated using biolayer interferometry and fluorescence anisotropy-based assays. Their potency to inhibit CK2 kinase activity was determined using the bioluminescent ADP-Glo assay. These experiments allowed us to investigate which chemical modifications prevent the binding of the compounds at the CK2α/CK2β interface. Seven out of sixteen compounds conserved the ability to bind at the protein-protein interface, among which three compounds exhibited better interface inhibition compared to CCH507. PubMed: 39835439DOI: 10.1002/cmdc.202400868 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.82 Å) |
Structure validation
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