5OTQ
The crystal structure of CK2alpha in complex with compound 33
Summary for 5OTQ
| Entry DOI | 10.2210/pdb5otq/pdb |
| Descriptor | Casein kinase II subunit alpha, ACETATE ION, 2-(1~{H}-benzimidazol-2-yl)-~{N}-[[4-(2-ethylphenyl)-3-methoxy-phenyl]methyl]ethanamine, ... (4 entities in total) |
| Functional Keywords | ck2alpha, ck2a, fragment based drug discovery, high concentration screening, selective atp competitive inhibitors, surface entrophy reduction, transferase |
| Biological source | Homo sapiens (Human) |
| Cellular location | Nucleus : P68400 |
| Total number of polymer chains | 1 |
| Total formula weight | 41675.49 |
| Authors | Brear, P.,De Fusco, C.,Iegre, J.,Yoshida, M.,Mitchell, S.,Rossmann, M.,Carro, L.,Sore, H.,Hyvonen, M.,Spring, D. (deposition date: 2017-08-22, release date: 2018-02-28, Last modification date: 2024-01-17) |
| Primary citation | Iegre, J.,Brear, P.,De Fusco, C.,Yoshida, M.,Mitchell, S.L.,Rossmann, M.,Carro, L.,Sore, H.F.,Hyvonen, M.,Spring, D.R. Second-generation CK2 alpha inhibitors targeting the alpha D pocket. Chem Sci, 9:3041-3049, 2018 Cited by PubMed Abstract: CK2 is a critical cell cycle regulator that also promotes various anti-apoptotic mechanisms. Development of ATP-non-competitive inhibitors of CK2 is a very attractive strategy considering that the ATP binding site is highly conserved among other kinases. We have previously utilised a pocket outside the active site to develop a novel CK2 inhibitor, . Whilst bound to this new pocket it was also interacting with the ATP site: herein, we describe an example of a CK2α inhibitor that binds completely outside the active site. This second generation αD-site binding inhibitor, compound (IC = 7 μM, GI = 10.0 ± 3.6 μM), has numerous advantages over the previously reported , including a reduction in the number of rotatable bonds, the absence of amide groups susceptible to the action of proteases and improved cellular permeability. Unlike with , there was no need to facilitate cellular uptake by making a prodrug. Moreover, displayed no drop off between its ability to inhibit the kinase (IC) and the ability to inhibit cell proliferation (GI). PubMed: 29732088DOI: 10.1039/c7sc05122k PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.38 Å) |
Structure validation
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