Journal
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
Volume 1780, Issue 12, Pages 1412-1420Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbagen.2008.06.010
Keywords
Protein kinase CK2; Inhibitor; Salicylaldehyde; Docking; Molecular modeling
Categories
Funding
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- Centre National pour la Recherche Scientifique (CNRS)
- Commissariat q l'Energie atomique (CEA)
- Institut Curie, the Ligue Nationale Contre le Cancer
- Institut National du Cancer [57]
- HPLC
- ChemAxon company
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Protein kinase CK2 is a Ser/Thr kinase, with a constitutive activity, that is considered as a promising target for cancer therapy. The currently available CK2 inhibitors lack the potency and the pharmacological properties necessary to be suitable and successful in clinical settings. We report the development of new potent CK2 inhibitors from salicylaidehyde derivatives identified by automated screening of a proprietary small-molecule library. Docking simulations and analysis of the structure-activity relationship for the hits allowed to determine their binding modes on CK2, and to carry out the optimization of their structures. This strategy led to the discovery of potent CK2 inhibitors with novel structures, one of which was able to inhibit CK2 activity in living cells and promote tumor cell death. The essential features required for potent CK2 inhibitory activity of this class of compounds are discussed. (C) 2008 Elsevier B.V. All rights reserved.
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