Paul Brear, Darby Ball, Katherine Stott, Sheena D’Arcy and Marko Hyvönen
Journal of Medicinal Chemistry: 63, 21, 12786–12798 (2020)
DOI: 0.1021/acs.jmedchem.0c01173
PDB coordinates:
6YPH (3D view),6YPK (3D view),6YPJ (3D view),6YPN (3D view)
Abstract
CK2α is a ubiquitous, well-studied kinase that is a target for small-molecule inhibition, for treatment of cancers. While many different classes of ATP-competitive inhibitors have been described for CK2α, they tend to suffer from significant off-target activity and new approaches are needed. A series of inhibitors of CK2α has recently been described as allosteric, acting at a previously unidentified binding site. Given the similarity of these inhibitors to known ATP-competitive inhibitors, we have investigated these further. In our thorough structural and biophysical analyses, we have found no evidence that these inhibitors bind to the proposed allosteric site. Continue reading →