RX-207, a Small Molecule Inhibitor of Protein Interaction with Glycosaminoglycans (SMIGs), Reduces Experimentally Induced Inflammation and Increases Survival Rate in Cecal Ligation and Puncture (CLP)-Induced Sepsis

Stefan Juhas, Nicholas Harris, Gabriela Il’kova, Pavol Rehák, Ferenc Zsila, Faina Yurgenzon Kogan, Orly Lahmy, Regina Zhuk, Paul Gregor, Juraj Koppel

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2 Citations (Scopus)

Abstract

The fused quinazolinone derivative, RX-207, is chemically and functionally related to small molecule inhibitors of protein binding to glycosaminoglycans (SMIGs). Composed of a planar aromatic amine scaffold, it inhibits protein binding to glycosaminoglycans (GAGs). RX-207 reduced neutrophil migration in thioglycollate-induced peritonitis (37%), inhibited carrageenan-induced paw edema (32%) and cerulein-induced pancreatitis (28%), and increased animal survival in the mouse model of cecal ligation and puncture (CLP)-induced sepsis (60%). The mechanism of RX-207 action, analyzed by UV spectroscopy, confirmed that which was elucidated for chemically related anti-inflammatory SMIGs. RX-207 binding to cell surface GAGs can account for the inhibition of neutrophil recruitment via the micro-vasculature and as a consequence, the reduction of neutrophil mediated tissue damage in the animal models of inflammation and improved survival of mice in CLP-induced sepsis.

Original languageEnglish
Pages (from-to)307-314
Number of pages8
JournalInflammation
Volume41
Issue number1
DOIs
Publication statusPublished - Feb 1 2018

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Keywords

  • glycosaminoglycan
  • heparin binding protein
  • inflammation
  • neutrophil
  • sepsis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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