9TTA

Crystal Structure of S12 bound to Ck2a

This is a non-PDB format compatible entry.

Summary for 9TTA

• Entry DOI: 10.2210/pdb9tta/pdb
• Descriptor: Casein kinase II subunit alpha, 3-[2-[4-[(3-chloranyl-4-phenyl-phenyl)methylamino]butyl-[2-oxidanylidene-2-[2-(2-prop-2-ynoxyethoxy)ethylamino]ethyl]amino]ethanoylamino]benzoic acid, ACETATE ION, ... (4 entities in total)
• Functional Keywords: protacs, hydrolase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 39739.61

Authors

Brear, P.,Day-Riley, S.,Krajcovicov, S.,Raj Sokha, A.,Venne, J.,Hyvonen, M.,Whitehurst, B.,Spring, D.R. (deposition date: 2026-01-06, release date: 2026-05-06, Last modification date: 2026-05-27)

Primary citation

Day-Riley, S.,Krajcovicova, S.,Sokhal, A.R.,Venne, J.L.,Brear, P.,Hyvonen, M.,Whitehurst, B.C.,Carroll, J.S.,Spring, D.R.
Towards the targeted protein degradation of CK2: design and synthesis of CAM4066-based PROTACs.
Beilstein J Org Chem, 22:611-619, 2026

PubMed Abstract: Human protein kinase CK2 is a constitutively active serine/threonine kinase implicated in numerous cancers. Although ATP-competitive inhibitors such as CX-4945 show therapeutic potential, they are limited by off-target effects and incomplete or transient CK2 suppression. PROTACs offer an alternative strategy by inducing proteasome-mediated degradation, with potential advantages in potency, selectivity, and duration of action. Herein, a series of CK2-targeting PROTACs has been designed and synthesised. By conjugating a CAM4066-derived warhead to CRBN or VHL ligands, four VHL-recruiting PROTACs, were prepared using PEG and alkyl linkers, alongside two CRBN-recruiting analogues featuring constrained linkers. A ligand-linker analogue in which a linker is projected from the solvent-exposed region of CK2α retained binding affinity comparable to CAM4066, confirming that linker installation is tolerated and preserves key interactions in the αD and ATP sites.

PubMed: 42125065
DOI: 10.3762/bjoc.22.47

Experimental method

X-RAY DIFFRACTION (1.91 Å)