Evaluation of 4,5,6,7-tetrahalogeno-1H-isoindole-1,3(2H)-diones as inhibitors of human protein kinase CK2

Biochim Biophys Acta. 2008 Jan;1784(1):143-9. doi: 10.1016/j.bbapap.2007.10.009. Epub 2007 Nov 20.


Protein kinase CK2 (Casein Kinase 2) is an extremely pleiotropic Ser/Thr kinase with high constitutive activity. The observation of CK2 deregulations in various pathological processes suggests that CK2 inhibitors may have a therapeutic value, particularly as anti-neoplastic and antiviral drugs. Here, we present the 4,5,6,7-tetrahalogeno-1H-isoindole-1,3(2H)-diones as a novel potent class of CK2 inhibitors. We identified this class of inhibitors by high-throughput docking of a compound collection in the ATP-binding site of human CK2. The most active compounds are 2-(4,5,6,7-tetraiodo-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propanoic acid and 2-(4,5,6,7-tetraiodo-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetic acid with IC(50) values of 0.15 microM and 0.3 microM, respectively. These inhibitors are ATP-competitive and they only minimally inhibit the activities of protein kinases DYRK1a, MSK1, GSK3 and CDK5. Binding modes for the most active inhibitors are proposed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Casein Kinase II / antagonists & inhibitors*
  • Casein Kinase II / chemistry
  • Casein Kinase II / metabolism*
  • Humans
  • Isoindoles / chemistry
  • Isoindoles / metabolism*
  • Isoindoles / pharmacology*
  • Molecular Structure
  • Protein Binding
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / metabolism*
  • Protein Kinase Inhibitors / pharmacology*
  • Recombinant Proteins


  • Isoindoles
  • Protein Kinase Inhibitors
  • Recombinant Proteins
  • Casein Kinase II