Identification of nonpeptidic small-molecule inhibitors of interleukin-2

Bioorg Med Chem Lett. 2005 Feb 15;15(4):983-7. doi: 10.1016/j.bmcl.2004.12.045.

Abstract

The identification, design, and synthesis of a series of novel sulfamide- and urea-based small-molecule antagonists of the protein-protein interaction IL-2/IL-2Ralpha are described. Installation of a furan carboxylic acid fragment onto a low-micromolar sulfamide resulted in a 23-fold improvement in activity, providing a sub-micromolar, nonpeptidic IL-2 inhibitor (IC(50)=0.60 microM).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Inhibitory Concentration 50
  • Interleukin-2 / antagonists & inhibitors*
  • Interleukin-2 / metabolism
  • Models, Molecular
  • Protein Binding / drug effects
  • Receptors, Interleukin-2 / metabolism
  • Structure-Activity Relationship
  • Sulfonic Acids / chemistry
  • Sulfonic Acids / pharmacology
  • Urea / chemistry
  • Urea / pharmacology

Substances

  • Interleukin-2
  • Receptors, Interleukin-2
  • Sulfonic Acids
  • Urea
  • sulfamic acid