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

0486791 - ÚŽFG 2019 RIV US eng J - Journal Article
Juhás, Štefan - Harris, N. - Ilková, G. - Rehák, P. - Zsila, F. - Kogan, F. Y. - Lahmy, O. - Zhuk, R. - Gregor, P. - Koppel, J.
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.
Inflammation. Roč. 41, č. 1 (2018), s. 307-314. ISSN 0360-3997. E-ISSN 1573-2576
Institutional support: RVO:67985904
Keywords : heparin binding protein * glycosaminoglycan * neutrophil
OECD category: Genetics and heredity (medical genetics to be 3)
Impact factor: 2.939, year: 2018

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.
Permanent Link: http://hdl.handle.net/11104/0281511