Many diseases, such as cancers, are related to the deregulation of the protein kinase CK2, which is why medical research aims to inhibit this enzyme. However, CK2 inhibitors developed so far act indiscriminately on most protein kinases, which can lead to adverse effects.
To develop new anticancer treatments, researchers at Irig target the selective inhibition of protein kinase CK2.
Researchers at Irig and the Faculty of Pharmacy in Lyon have successfully synthesized and characterized the AB668 molecule, which inhibits the activity of CK2 with high specificity. Indeed, this bivalent molecule simultaneously binds to the catalytic site of CK2 and an adjacent hydrophobic pocket, providing it with a unique inhibition mechanism.
Moreover, the AB668 molecule does not show adverse side effects as it induces apoptosis in numerous cell lines derived from aggressive cancers (kidney, breast, melanoma, pancreas, colon), while sparing healthy cells.
Therefore, the AB668 molecule could represent a promising new anti-cancer agent. The next step will be to test the molecule after its optimization through medicinal chemistry, in pre-clinical models of various cancers.
The AB668 molecule (blue) exclusively inhibits the CK2 protein by simultaneously binding to its catalytic site and an adjacent hydrophobic pocket.
AB668 induces apoptosis in tumor cells while preserving healthy cells.
Bancet A, Frem R, Jeanneret F, Mularoni A, Bazelle P, Roelants R, Delcros JG, Guichou JF, Pillet C, Coste I, Renno T, Battail C, Cochet C, Lomberget T, Filhol O and Krimm I.
Cancer selective cell death induction by a bivalent CK2 inhibitor targeting the ATP site and the allosteric
αD pocket.
iScience 2024.