Generation of potent and selective kinase inhibitors by combinatorial biosynthesis of glycosylated indolocarbazoles

Chem Commun (Camb). 2009 Jul 21;(27):4118-20. doi: 10.1039/b905068j. Epub 2009 May 27.

Abstract

We report the generation of novel glycosylated indolocarbazoles by combinatorial biosynthesis, and the identification of two novel potent and selective compounds inhibitors of JAK2 and Ikkb kinases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Carbazoles / chemistry*
  • Carbazoles / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Combinatorial Chemistry Techniques / methods*
  • Humans
  • Indole Alkaloids / chemistry*
  • Indole Alkaloids / pharmacology
  • Molecular Structure
  • Multigene Family
  • Plasmids
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology
  • Staurosporine / analogs & derivatives
  • Staurosporine / biosynthesis
  • Staurosporine / chemistry
  • Staurosporine / pharmacology
  • Streptomyces / enzymology
  • Streptomyces / genetics*

Substances

  • Antineoplastic Agents
  • Carbazoles
  • Indole Alkaloids
  • Protein Kinase Inhibitors
  • arcyriaflavin A
  • rebeccamycin
  • Staurosporine