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
| Autor: | Gabriela Il'ková, Paul Gregor, Orly Lahmy, Ferenc Zsila, Faina Yurgenzon Kogan, Nicholas Harris, Pavol Rehák, Stefan Juhas, Regina Zhuk, Juraj Koppel |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Neutrophils Immunology Cell Anti-Inflammatory Agents Peritonitis Inflammation Plasma protein binding Punctures Sepsis Glycosaminoglycan 03 medical and health sciences medicine Cell Adhesion Immunology and Allergy Animals Edema Cecum Ligation Glycosaminoglycans Quinazolinones chemistry.chemical_classification Mice Inbred BALB C Chemistry Aromatic amine medicine.disease Small molecule Molecular biology Disease Models Animal 030104 developmental biology medicine.anatomical_structure Biochemistry Neutrophil Infiltration Pancreatitis medicine.symptom Protein Binding |
| Zdroj: | Inflammation. 41(1) |
| ISSN: | 1573-2576 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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