Novel potent dual inhibitors of CK2 and Pim kinases with antiproliferative activity against cancer cells

A novel family of potent dual inhibitors of CK2 and the Pim kinases was discovered by modifying the scaffolds of tricyclic Pim inhibitors. Several analogs were active at single digit nanomolar IC50 values against CK2 and the Pim isoforms Pim-1 and Pim-2. The molecules displayed antiproliferative act...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2012-05, Vol.22 (9), p.3327-3331
Hauptverfasser:	Pierre, Fabrice, Regan, Collin F., Chevrel, Marie-Claire, Siddiqui-Jain, Adam, Macalino, Diwata, Streiner, Nicole, Drygin, Denis, Haddach, Mustapha, O’Brien, Sean E., Rice, William G., Ryckman, David M.
Format:	Artikel
Sprache:	eng
Schlagworte:	Antineoplastic agents Antineoplastic Agents - pharmacology Biological and medical sciences Cancer Casein Kinase II - antagonists & inhibitors Cell Line, Tumor Cell Proliferation - drug effects chemistry CK2 Drug Discovery drugs General pharmacology Humans Inhibitory Concentration 50 Kinase inhibitor Medical sciences Multikinase inhibitors Neoplasms - drug therapy Neoplasms - pathology Pharmacology. Drug treatments phenotype phosphotransferases (kinases) Physicochemical properties. Structure-activity relationships Pim Protein Kinase Inhibitors - pharmacology Proto-Oncogene Proteins c-pim-1 - antagonists & inhibitors
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Zusammenfassung:	A novel family of potent dual inhibitors of CK2 and the Pim kinases was discovered by modifying the scaffolds of tricyclic Pim inhibitors. Several analogs were active at single digit nanomolar IC50 values against CK2 and the Pim isoforms Pim-1 and Pim-2. The molecules displayed antiproliferative activity in various cell phenotypes in the low micromolar and submicromolar range, providing an excellent starting point for further drug discovery optimization.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2012.02.099