Chelerythrine is a potent and specific inhibitor of protein kinase C

Biochem Biophys Res Commun. 1990 Nov 15;172(3):993-9. doi: 10.1016/0006-291x(90)91544-3.


The benzophenanthridine alkaloid chelerythrine is a potent, selective antagonist of the Ca++/phospholopid-dependent protein kinase (Protein kinase C: PKC) from the rat brain. Half-maximal inhibition of the kinase occurs at 0.66 microM. Chelerythrine interacted with the catalytic domain of PKC, was a competitive inhibitor with respect to the phosphate acceptor (histone IIIS) (Ki = 0.7 microM) and a non-competitive inhibitor with respect to ATP. This effect was further evidenced by the fact that chelerythrine inhibited native PKC and its catalytic fragment identically and did not affect [3H]- phorbol 12,13 dibutyrate binding to PKC. Chelerythrine selectively inhibited PKC compared to tyrosine protein kinase, cAMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase. The potent antitumoral activity of celerythrine measured in vitro might be due at least in part to inhibition of PKC and thus suggests that PKC may be a model for rational design of antitumor drugs.

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Alkaloids / pharmacology
  • Animals
  • Antibiotics, Antineoplastic / pharmacology*
  • Benzophenanthridines
  • Binding, Competitive
  • Brain / drug effects
  • Brain / enzymology*
  • Cell Transformation, Neoplastic
  • Isoquinolines / pharmacology
  • Kinetics
  • Leukemia L1210 / drug therapy
  • Leukemia L1210 / pathology
  • Lymphoma / drug therapy
  • Lymphoma / enzymology
  • Phenanthridines / pharmacology*
  • Piperazines / pharmacology
  • Protein Kinase C / antagonists & inhibitors*
  • Rats
  • Staurosporine
  • Tumor Cells, Cultured


  • Alkaloids
  • Antibiotics, Antineoplastic
  • Benzophenanthridines
  • Isoquinolines
  • Phenanthridines
  • Piperazines
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • chelerythrine
  • Protein Kinase C
  • Staurosporine