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Novel non-ATP competitive small molecules targeting the CK2 α/β interface
DOI:
10.1016/j.bmc.2018.05.011
Authors:
Paul
Brear
(University of Cambridge)
,
Andrew
North
(University of Cambridge)
,
Jessica
Iegre
(University of Cambridge)
,
Kathy
Hadje Georgiou
(University of Cambridge)
,
Alexandra
Lubin
(University of Cambridge)
,
Laura
Carro
(University of Cambridge)
,
William
Green
(University of Cambridge)
,
Hannah F.
Sore
(University of Cambridge)
,
Marko
Hyvonen
(University of Cambridge)
,
David R.
Spring
(University of Cambridge)
Co-authored by industrial partner:
No
Type:
Journal Paper
Journal:
Bioorganic & Medicinal Chemistry
State:
Published (Approved)
Published:
May 2018
Diamond Proposal Number(s):
9537

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 CK2α and CK2β at the α-β interface of the holoenzyme. A fragment, CAM187, with an IC50 of 44 μM 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 CK2α. The fragment-like molecules discovered in this study represent unique scaffolds to CK2 inhibition and leave room for further optimisation.
Journal Keywords: CK2; Protein-protein interaction; Fragment based drug discovery
Subject Areas:
Biology and Bio-materials,
Chemistry,
Medicine
Instruments:
I24-Microfocus Macromolecular Crystallography
Other Facilities: ESRF
Added On:
22/05/2018 10:23
Documents:
1-s2.0-S0968089618303298-main.pdf
Discipline Tags:
Non-Communicable Diseases
Health & Wellbeing
Cancer
Biochemistry
Chemistry
Structural biology
Organic Chemistry
Drug Discovery
Life Sciences & Biotech
Technical Tags:
Diffraction
Macromolecular Crystallography (MX)