Summary for 9QQX
| Entry DOI | 10.2210/pdb9qqx/pdb |
| Descriptor | Casein kinase II subunit alpha, 5-[2-[4-[[3-aminocarbonyl-5-(trifluoromethyloxy)phenyl]methylamino]butoxy]ethylamino]benzo[c][2,6]naphthyridine-8-carboxamide, ACETATE ION, ... (4 entities in total) |
| Functional Keywords | fragment based drug discovery, kinase, hydrolase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 39661.00 |
| Authors | Brear, P.,Glossop, P.,Pandey, S.,Hyvonen, M.,Spring, D.,Butt, R.,Cawkill, D. (deposition date: 2025-04-02, release date: 2025-10-22, Last modification date: 2025-11-05) |
| Primary citation | Glossop, P.A.,Brear, P.,Wright, S.,Flanagan, N.,Glossop, M.S.,Lane, C.A.L.,Butt, R.P.,Spring, D.R.,Hyvonen, M.,Cawkill, D. Exploiting the Cryptic alpha D Pocket of Casein Kinase 2 alpha (CK2 alpha ) to Deliver Highly Potent and Selective Type 1 Inhibitors. J.Med.Chem., 68:21587-21614, 2025 Cited by PubMed Abstract: Casein kinase 2α (CK2α) is an oncology drug target that acts as a positive regulator of many tumorigenic signaling pathways. We previously reported that CK2α has a unique cryptic binding site, the αD pocket, that offers the potential for inhibitors with improved kinase selectivity. The prototype bivalent molecule CAM4066 () confirmed that improved selectivity could be achieved while binding in both the ATP-binding site and the αD pocket. A drug discovery project to develop a new series of bivalent CK2α inhibitors with increased cell potency and selectivity identified (APL-5125), a highly potent, ATP-competitive CK2α inhibitor with exquisite kinase selectivity and cellular potency. Compound demonstrates inhibition of p-AKT S129 in tumors (HCT116) following once-daily oral administration and shows a clear PK-PD relationship with unbound drug exposure. has a superior preclinical profile to existing CK2α inhibitors and is currently under evaluation in patients with advanced solid tumors. PubMed: 41085029DOI: 10.1021/acs.jmedchem.5c01807 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.6 Å) |
Structure validation
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