Summary for 9HPH
| Entry DOI | 10.2210/pdb9hph/pdb |
| Descriptor | Casein kinase II subunit alpha, SULFATE ION, DI(HYDROXYETHYL)ETHER, ... (6 entities in total) |
| Functional Keywords | protein kinase ck2 inhibitor cancer, transferase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 89421.86 |
| Authors | |
| Primary citation | Marlhoux, L.,Arnaud, A.,Hervieu, C.,Makulyte, G.,Martinasso, C.,Mularoni, A.,Delcros, J.G.,Krimm, I.,Hernandez-Vargas, H.,Ichim, G.,Meurette, O.,Neves, D.,Bancet, A. Discovery of KDX1381, a Bivalent CK2 alpha Inhibitor for the Treatment of Solid Tumors as a Single Agent or in Combination. J.Med.Chem., 68:12819-12844, 2025 Cited by PubMed Abstract: Casein kinase 2 (CK2) has emerged as a promising therapeutic target across a broad spectrum of malignancies, including pediatric and orphan cancers. The identification of a ligandable allosteric αD pocket on the CK2α subunit has enabled the development of bivalent inhibitors, which bind simultaneously to both the adenosine triphosphate (ATP) site and the allosteric pocket. Here, we report the discovery and pharmacological characterization of , a structure-guided bivalent CK2α inhibitor with low-nanomolar potency and high selectivity, confirmed by cocrystal structures. In mice, suppressed CK2-driven tumor growth as a monotherapy and enhanced therapeutic efficacy when combined with vascular endothelial growth factor receptor (VEGFR) inhibitors or DNA-damaging agents in hepatocellular carcinoma and glioma models. These findings support bivalent CK2α inhibition as a differentiated therapeutic strategy with broad applicability in CK2-dependent cancers. PubMed: 40493957DOI: 10.1021/acs.jmedchem.5c00695 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.16 Å) |
Structure validation
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