Natural product inhibitors of protein-protein interactions mediated by Src-family SH2 domains

Bioorg Med Chem Lett. 2009 Jun 15;19(12):3305-9. doi: 10.1016/j.bmcl.2009.04.083. Epub 2009 Apr 23.

Abstract

In this Letter, we report the natural products salvianolic acid A, salvianolic acid B, and caftaric acid as inhibitors of the protein-protein interactions mediated by the SH2 domains of the Src-family kinases Src and Lck, two established disease targets. Moreover, we propose a binding mode for the inhibitors based on molecular modeling, which will facilitate chemical optimization efforts of these important lead structures for drug discovery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzofurans / pharmacology
  • Biological Products / pharmacology*
  • Caffeic Acids / pharmacology
  • Drug Discovery
  • Humans
  • Lactates / pharmacology
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / antagonists & inhibitors
  • Models, Molecular
  • Phenols / pharmacology
  • Protein Binding / drug effects
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins pp60(c-src) / antagonists & inhibitors
  • src Homology Domains / drug effects*
  • src-Family Kinases / antagonists & inhibitors*

Substances

  • Benzofurans
  • Biological Products
  • Caffeic Acids
  • Lactates
  • Phenols
  • Protein Kinase Inhibitors
  • salvianolic acid A
  • salvianolic acid B
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Proto-Oncogene Proteins pp60(c-src)
  • src-Family Kinases
  • caftaric acid