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.

Biomolecular Self Assembly Group Institute of Materials and Environmental Chemistry Research Centre for Natural Sciences Hungarian Academy of Sciences Budapest Hungary

Ephraim Katzir Department of Biotechnology Engineering ORT Braude Academic College of Engineering Snonit 51 2161002 Karmiel Israel

GISMO Therapeutics Inc A253 ASTECC UK Lexington KY 40506 USA

GYN FIV a s Záhradnícka 42 821 085 Bratislava Slovakia

Institute of Animal Physiology and Genetics of the ASCR v v i Rumburská 89 277 21 Libechov Czech Republic

Institute of Animal Physiology Slovak Academy of Sciences 04001 Kosice Slovakia

Rimonyx Pharmaceuticals Ltd Rabin Science Park 70400 Ness Ziona Israel

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