Formylchromone derivatives as irreversible and selective inhibitors of human protein tyrosine phosphatase 1B. Kinetic and modeling studies

Bioorg Med Chem. 2005 Feb 15;13(4):1325-32. doi: 10.1016/j.bmc.2004.11.006.

Abstract

A series of formylchromone derivatives were synthesized as PTP1B inhibitors and some of them were potent against PTP1B with IC50 values as low as 1.0 microM. They exhibited remarkable selectivity for PTP1B over other human PTPases. Kinetic studies revealed that formylchromone derivatives are irreversible and active site-directed inhibitors. Molecular modeling study identified the orientation of the inhibitor bound at the active site of PTP1B.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromones / chemistry
  • Chromones / pharmacology*
  • Crystallography, X-Ray
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Kinetics
  • Models, Molecular
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Chromones
  • Enzyme Inhibitors
  • formylchromone
  • PTPN1 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases