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.

• Keywords
• glycosaminoglycan, heparin binding protein, inflammation, neutrophil, sepsis,
• MeSH
• Anti-Inflammatory Agents pharmacology   MeSH
• Cell Adhesion drug effects   MeSH
• Cecum microbiology   surgery   MeSH
• Quinazolinones pharmacology   MeSH
• Edema chemically induced   metabolism   pathology   prevention & control   MeSH
• Glycosaminoglycans metabolism   MeSH
• Neutrophil Infiltration drug effects   MeSH
• Ligation MeSH
• Disease Models, Animal MeSH
• Mice, Inbred BALB C MeSH
• Neutrophils drug effects   metabolism   microbiology   MeSH
• Pancreatitis chemically induced   metabolism   pathology   prevention & control   MeSH
• Peritonitis chemically induced   metabolism   pathology   prevention & control   MeSH
• Punctures MeSH
• Sepsis metabolism   microbiology   pathology   prevention & control   MeSH
• Protein Binding MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anti-Inflammatory Agents MeSH
• Quinazolinones MeSH
• Glycosaminoglycans MeSH