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PDBsum entry 5cu0
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References listed in PDB file
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Key reference
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Title
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A fragment-Based approach leading to the discovery of a novel binding site and the selective ck2 inhibitor cam4066.
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Authors
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C.De fusco,
P.Brear,
J.Iegre,
K.H.Georgiou,
H.F.Sore,
M.Hyvönen,
D.R.Spring.
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Ref.
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Bioorg Med Chem, 2017,
25,
3471-3482.
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PubMed id
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Abstract
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Recently we reported the discovery of a potent and selective CK2α inhibitor
CAM4066. This compound inhibits CK2 activity by exploiting a pocket located
outside the ATP binding site (αD pocket). Here we describe in detail the
journey that led to the discovery of CAM4066 using the challenging fragment
linking strategy. Specifically, we aimed to develop inhibitors by linking a
high-affinity fragment anchored in the αD site to a weakly binding warhead
fragment occupying the ATP site. Moreover, we describe the remarkable impact
that molecular modelling had on the development of this novel chemical tool. The
work described herein shows potential for the development of a novel class of
CK2 inhibitors.
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