Cancer selective cell death induction by a bivalent CK2 inhibitor targeting the ATP site and the allosteric αD pocket - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue iScience Année : 2024

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

Caroline Roelants
  • Fonction : Auteur
Catherine Pillet
  • Fonction : Auteur
Toufic Renno
Claude Cochet
  • Fonction : Auteur
Odile Filhol

Résumé

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
Fichier principal
Vignette du fichier
1-s2.0-S258900422400124X-main.pdf (4.79 Mo) Télécharger le fichier
Origine Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

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

Identifiants

Citer

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⟩
7 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More