Autor: Sokhal, A. R.; Krajcovicova, S.; Iegre, J.; Brear, P.; De Fusco, C.; Glossop, P. A.; Cawkill, D.; Hyvonen, M.; Spring, D. R.
Název práce v češtině: –
Název práce v angličtině: Selective Inhibition of CK2: Emerging Strategies and Future Directions
Studentská publikace: ne
Klíčová slova v češtině: –
Klíčová slova v angličtině: –
Abstrakt česky: –
Abstrakt anglicky: CK2 is a constitutively active serine/threonine kinase implicated in cancer, viral infection, and neurodegeneration, but its conserved ATP-binding site and complex holoenzyme assembly have long made selective inhibition challenging. This Perspective discusses three complementary strategies for selective CK2 inhibition: targeting the CK2α/β interface with small molecules, disrupting the same interface with conformationally constrained peptides, and exploiting the cryptic αD pocket for dual-site inhibitor design. CK2α/β-interface inhibitors, including CAM187, CAM7117 and P8C9, established structurally validated routes to modulate holoenzyme assembly and β-dependent substrate phosphorylation. Validation of the αD pocket as a ligandable cryptosteric site enabled dual-site ligands such as CAM4066 and αD-directed inhibitors such as CAM4712, followed by related advances including AB668, KDX1381 and Biv5. These efforts culminated in APL-5125, a highly selective, subnanomolar dual-site inhibitor now in Phase 1/2 clinical evaluation.
Jazyk v originále: english
Název časopisu: J. Med. Chem.
Rok: 2026
Svazek (ročník): 69
Číslo časopisu v rámci uvedeného svazku: 15
Strana od-do: 17584–17601
Impact factor: 7.3
Q1: ano

ISSN časopisu: –
Vydavatel: American Chemical Society
Způsob financování: GA CR 22-07138O
DOI: https://doi.org/10.1021/acs.jmedchem.6c00643