7L1X
Structure of human CK2 alpha kinase (catalytic subunit) with the inhibitor 108600.
Summary for 7L1X
| Entry DOI | 10.2210/pdb7l1x/pdb |
| Descriptor | Casein kinase II subunit alpha, SULFATE ION, GLYCEROL, ... (5 entities in total) |
| Functional Keywords | inhibitor 108600, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 40950.29 |
| Authors | Rechkoblit, O.,Aggarwal, A.K. (deposition date: 2020-12-15, release date: 2021-08-11, Last modification date: 2023-10-18) |
| Primary citation | Sato, K.,Padgaonkar, A.A.,Baker, S.J.,Cosenza, S.C.,Rechkoblit, O.,Subbaiah, D.R.C.V.,Domingo-Domenech, J.,Bartkowski, A.,Port, E.R.,Aggarwal, A.K.,Ramana Reddy, M.V.,Irie, H.Y.,Premkumar Reddy, E. Simultaneous CK2/TNIK/DYRK1 inhibition by 108600 suppresses triple negative breast cancer stem cells and chemotherapy-resistant disease. Nat Commun, 12:4671-4671, 2021 Cited by PubMed Abstract: Triple negative breast cancer (TNBC) remains challenging because of heterogeneous responses to chemotherapy. Incomplete response is associated with a greater risk of metastatic progression. Therefore, treatments that target chemotherapy-resistant TNBC and enhance chemosensitivity would improve outcomes for these high-risk patients. Breast cancer stem cell-like cells (BCSCs) have been proposed to represent a chemotherapy-resistant subpopulation responsible for tumor initiation, progression and metastases. Targeting this population could lead to improved TNBC disease control. Here, we describe a novel multi-kinase inhibitor, 108600, that targets the TNBC BCSC population. 108600 treatment suppresses growth, colony and mammosphere forming capacity of BCSCs and induces G2M arrest and apoptosis of TNBC cells. In vivo, 108600 treatment of mice bearing triple negative tumors results in the induction of apoptosis and overcomes chemotherapy resistance. Finally, treatment with 108600 and chemotherapy suppresses growth of pre-established TNBC metastases, providing additional support for the clinical translation of this agent to clinical trials. PubMed: 34344863DOI: 10.1038/s41467-021-24878-z PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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