Endoxifen is a new potent inhibitor of PKC: a potential therapeutic agent for bipolar disorder

Bioorg Med Chem Lett. 2010 Apr 15;20(8):2665-7. doi: 10.1016/j.bmcl.2010.02.024. Epub 2010 Feb 23.

Abstract

Protein kinase C (PKC) plays a major role in regulation of both pre and postsynaptic neurotransmission. Excessive activation of PKC results in symptoms related to bipolar disorder. Tamoxifen, a widely used breast cancer drug is known to inhibit PKC and demonstrate antimanic properties in human. We describe herein the synthesis of endoxifen, a tamoxifen active metabolite and compared its PKC inhibitory activity with that of tamoxifen. Endoxifen exhibited fourfold higher potency compared to tamoxifen.

MeSH terms

  • Animals
  • Magnetic Resonance Spectroscopy
  • Mice
  • Protein Kinase C / antagonists & inhibitors*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Rats
  • Tamoxifen / analogs & derivatives*
  • Tamoxifen / chemistry
  • Tamoxifen / pharmacology

Substances

  • Protein Kinase Inhibitors
  • Tamoxifen
  • 4-hydroxy-N-desmethyltamoxifen
  • Protein Kinase C