Small-molecule inhibitors of NADPH oxidase 4

J Med Chem. 2010 Sep 23;53(18):6758-62. doi: 10.1021/jm1004368.

Abstract

NOX enzymes are the major contributors in many oxidative damage related diseases. Unfortunately, at present no specific NOX inhibitor is available. Here, we describe the discovery and development of novel NOX4 inhibitors. Compound libraries were tested in a cell-based assay as a primary screen, monitoring H2O2 production. Twenty-four compounds inhibited Nox4 activity with low-micromolar IC(50) values of which three were selected for further drug development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminosalicylic Acids / chemistry
  • Aminosalicylic Acids / pharmacology
  • Cell Line
  • Flavonoids / chemistry
  • Flavonoids / pharmacology
  • Humans
  • Hydrogen Peroxide / metabolism
  • Indoles / chemistry
  • Indoles / pharmacology
  • Models, Molecular
  • NADPH Oxidase 4
  • NADPH Oxidases / antagonists & inhibitors*
  • Oxalates / chemistry
  • Oxalates / pharmacology
  • Phenanthrenes / chemical synthesis
  • Phenanthrenes / pharmacology
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology
  • Structure-Activity Relationship

Substances

  • Aminosalicylic Acids
  • Flavonoids
  • Indoles
  • Oxalates
  • Phenanthrenes
  • Pyrimidines
  • Hydrogen Peroxide
  • NADPH Oxidase 4
  • NADPH Oxidases
  • NOX4 protein, human