A novel small-molecule inhibitor of IL-6 signalling

Bioorg Med Chem Lett. 2010 Dec 1;20(23):7029-32. doi: 10.1016/j.bmcl.2010.09.117. Epub 2010 Sep 29.

Abstract

A small library of pyrrolidinesulphonylaryl molecules has been synthesized via an efficient 4-step route, and members evaluated for their ability to inhibit IL-6 signalling. One molecule (6a) was found to have promising activity against IL-6/STAT3 signalling at the low micromolar level, and to selectively inhibit phosphorylation of STAT3 (but not STAT1) in IL-6 stimulated MDA-MB-231 breast cancer and HeLa cell lines. It was also selectively cytostatic in MDA-MB-231 (STAT3-dependent) versus A4 (STAT3-null) cells suggesting STAT3-specific inhibitory properties.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cytostatic Agents / chemistry*
  • Cytostatic Agents / pharmacology
  • Female
  • HeLa Cells
  • Humans
  • Interleukin-6 / antagonists & inhibitors*
  • Phosphorylation / drug effects
  • Pyrrolidines / chemistry*
  • Pyrrolidines / pharmacology
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects*
  • Small Molecule Libraries
  • Structure-Activity Relationship
  • Sulfones

Substances

  • Cytostatic Agents
  • Interleukin-6
  • Pyrrolidines
  • STAT3 Transcription Factor
  • Small Molecule Libraries
  • Sulfones