K-252 Compounds, Novel and Potent Inhibitors of Protein Kinase C and Cyclic Nucleotide-Dependent Protein Kinases

Biochem Biophys Res Commun. 1987 Jan 30;142(2):436-40. doi: 10.1016/0006-291x(87)90293-2.

Abstract

K-252 compounds (K-252a and b isolated from Nocardiopsis sp. (1) and their synthetic derivatives) were found to inhibit cyclic nucleotide-dependent protein kinases and protein kinase C to various extents. The inhibitions were of the competitive type with respect to ATP. K-252a was a non-selective inhibitor for these three protein kinases with Ki values 18-25 nM. K-252b showed a comparable potency for protein kinase C (Ki, 20nM), whereas inhibitory potencies for cyclic nucleotide-dependent protein kinases were reduced. KT5720 and KT5822 selectively inhibited cAMP-dependent (Ki, 60nM) and cGMP-dependent (Ki, 2.4nM) protein kinases, respectively.

MeSH terms

  • Adenosine Triphosphate / pharmacology
  • Carbazoles / pharmacology*
  • Cyclic GMP / pharmacology
  • Indole Alkaloids
  • Protein Kinase C / antagonists & inhibitors*
  • Protein Kinase Inhibitors*
  • Structure-Activity Relationship

Substances

  • Carbazoles
  • Indole Alkaloids
  • Protein Kinase Inhibitors
  • Adenosine Triphosphate
  • staurosporine aglycone
  • Protein Kinase C
  • Cyclic GMP