Cancer selective cell death induction by a bivalent CK2 inhibitor targeting the ATP site and the allosteric αD pocket - Archive ouverte HAL
Journal Articles iScience Year : 2024

Cancer selective cell death induction by a bivalent CK2 inhibitor targeting the ATP site and the allosteric αD pocket

Caroline Roelants
  • Function : Author
Catherine Pillet
  • Function : Author
Toufic Renno
Claude Cochet
  • Function : Author
Odile Filhol

Abstract

Although the involvement of protein kinase CK2 in cancer is well-documented, there is a need for selective CK2 inhibitors suitable for investigating CK2 specific roles in cancer-related biological pathways and further exploring its therapeutic potential. Here, we report the discovery of AB668, an outstanding selective inhibitor that binds CK2 through a bivalent mode, interacting both at the ATP site and an allosteric αD pocket unique to CK2. Using caspase activation assay, live-cell imaging, and transcriptomic analysis, we have compared the effects of this bivalent inhibitor to representative ATP-competitive inhibitors, CX-4945, and SGC-CK2-1. Our results show that in contrast to CX-4945 or SGC-CK2-1, AB668, by targeting the CK2 αD pocket, has a distinct mechanism of action regarding its anti-cancer activity, inducing apoptotic cell death in several cancer cell lines and stimulating distinct biological pathways in renal cell carcinoma
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Dates and versions

hal-04424788 , version 1 (19-07-2024)

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Alexandre Bancet, Rita Frem, Florian Jeanneret, Angélique Mularoni, Pauline Bazelle, et al.. Cancer selective cell death induction by a bivalent CK2 inhibitor targeting the ATP site and the allosteric αD pocket. iScience, 2024, 27 (2), pp.108903. ⟨10.1016/j.isci.2024.108903⟩. ⟨hal-04424788⟩
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