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Novel non-ATP competitive small molecules targeting the CK2 ?/? interface.

ABSTRACT: Increased CK2 levels are prevalent in many cancers. Combined with the critical role CK2 plays in many cell-signaling pathways, this makes it a prime target for down regulation to fight tumour growth. Herein, we report a fragment-based approach to inhibiting the interaction between CK2? and CK2? at the ?-? interface of the holoenzyme. A fragment, CAM187, with an IC50 of 44??M and a molecular weight of only 257?gmol-1 has been identified as the most promising compound. Importantly, the lead fragment only bound at the interface and was not observed in the ATP binding site of the protein when co-crystallised with CK2?. The fragment-like molecules discovered in this study represent unique scaffolds to CK2 inhibition and leave room for further optimisation.

SUBMITTER: Brear P

PROVIDER: S-EPMC6562204 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Novel non-ATP competitive small molecules targeting the CK2 α/β interface.

Brear Paul P North Andrew A Iegre Jessica J Hadje Georgiou Kathy K Lubin Alexandra A Carro Laura L Green William W Sore Hannah F HF Hyvönen Marko M Spring David R DR

Bioorganic & medicinal chemistry 20180509 11

Increased CK2 levels are prevalent in many cancers. Combined with the critical role CK2 plays in many cell-signaling pathways, this makes it a prime target for down regulation to fight tumour growth. Herein, we report a fragment-based approach to inhibiting the interaction between CK2α and CK2β at the α-β interface of the holoenzyme. A fragment, CAM187, with an IC<sub>50</sub> of 44 μM and a molecular weight of only 257 gmol<sup>-1</sup> has been identified as the most promising compound. Import ...[more]

PMID: 29759799

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