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

Fabrice Pierre; Collin F Regan; Marie-Claire Chevrel; Adam Siddiqui-Jain; Diwata Macalino; Nicole Streiner; Denis Drygin; Mustapha Haddach; Sean E O'Brien; William G Rice; David M Ryckman

doi:10.1016/j.bmcl.2012.02.099

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

Bioorg Med Chem Lett. 2012 May 1;22(9):3327-31. doi: 10.1016/j.bmcl.2012.02.099. Epub 2012 Mar 6.

Authors

Fabrice Pierre¹, Collin F Regan, Marie-Claire Chevrel, Adam Siddiqui-Jain, Diwata Macalino, Nicole Streiner, Denis Drygin, Mustapha Haddach, Sean E O'Brien, William G Rice, David M Ryckman

Affiliation

¹ Cylene Pharmaceuticals, 5820 Nancy Ridge Drive, Suite 200, San Diego, CA 92121, USA. fpierre@cylenepharma.com

PMID: 22460033
DOI: 10.1016/j.bmcl.2012.02.099

Abstract

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 IC(50) 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.

MeSH terms

Antineoplastic Agents / pharmacology*
Casein Kinase II / antagonists & inhibitors*
Cell Line, Tumor
Cell Proliferation / drug effects*
Drug Discovery
Humans
Inhibitory Concentration 50
Neoplasms / drug therapy
Neoplasms / pathology*
Protein Kinase Inhibitors / pharmacology*
Proto-Oncogene Proteins c-pim-1 / antagonists & inhibitors*

Substances

Antineoplastic Agents
Protein Kinase Inhibitors
Casein Kinase II
Proto-Oncogene Proteins c-pim-1
proto-oncogene proteins pim