A derivative of staurosporine (CGP 41 251) shows selectivity for protein kinase C inhibition and in vitro anti-proliferative as well as in vivo anti-tumor activity

Int J Cancer. 1989 May 15;43(5):851-6. doi: 10.1002/ijc.2910430519.


Analogues of staurosporine were synthesized and their ability to inhibit protein kinases was examined. Staurosporine is a potent but non-selective inhibitor of in vitro protein kinase C(PKC) activity (IC50 6.0 nM). The derivative CGP 41 251 had reduced PKC activity with an IC50 of 50 nM but showed a high degree of selectivity when assayed for inhibition of cyclic AMP-dependent protein kinase (IC50 2.4 microM), S6 kinase (IC50 5.0 microM) and tyrosine-kinase-specific activity of epidermal growth factor receptor (IC50 3.0 microM). Staurosporine and CGP 41 251 exerted growth inhibition in the human bladder carcinoma line T-24, human promyelocytic leukemia line HL-60 and bovine corneal endothelial cells at concentrations which correlated well with in vitro PKC inhibition. In addition, both compounds inhibited the release of H2O2 from human monocytes pre-treated with 12-O-tetradecanoyl-phorbol-13-acetate at non-toxic concentrations. In vivo anti-tumor activity was examined in T-24 human bladder carcinoma xenografts in athymic nude mice. Tumor growth inhibition tests revealed significant anti-tumor activity (2p less than 0.001) at 1/10 of the maximum tolerated doses for both compounds. By contrast, a closely related derivative of staurosporine (CGP 42 700) was inactive at concentrations of over 100 microM in all in vitro enzyme and anti-proliferative assays as well as in animal tumor models. Our data suggest an association between PKC inhibition and anti-proliferative and anti-tumor activity.

Publication types

  • Retracted Publication

MeSH terms

  • Alkaloids / pharmacology*
  • Alkaloids / therapeutic use*
  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Brain / enzymology
  • Cell Line
  • ErbB Receptors / metabolism
  • Humans
  • Hydrogen Peroxide / blood
  • In Vitro Techniques
  • Mice
  • Mice, Nude
  • Monocytes / drug effects
  • Monocytes / physiology
  • Phosphorylase Kinase / metabolism
  • Phosphorylation
  • Protein Kinase C / antagonists & inhibitors*
  • Protein Kinase C / isolation & purification
  • Protein Kinases / isolation & purification
  • Protein Kinases / metabolism
  • Staurosporine
  • Swine
  • Tumor Cells, Cultured / cytology
  • Tumor Cells, Cultured / drug effects*
  • Urinary Bladder Neoplasms / drug therapy*


  • Alkaloids
  • Antineoplastic Agents
  • Hydrogen Peroxide
  • Protein Kinases
  • Phosphorylase Kinase
  • ErbB Receptors
  • Protein Kinase C
  • Staurosporine
  • midostaurin