Mechanism of action and efficacy of RX-111, a thieno[2,3-c]pyridine derivative and small molecule inhibitor of protein interaction with glycosaminoglycans (SMIGs), in delayed-type hypersensitivity, TNBS-induced colitis and experimental autoimmune encephalomyelitis

Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]
Nicholas HarrisPaul Gregor

Abstract

Elucidate the mechanism of action of the small molecule inhibitor of protein binding to glycosaminoglycans, RX-111 and assay its anti-inflammatory activity in animal models of inflammatory disease. The glycosaminoglycan, heparin, was used in the mechanism of action study of RX-111. Human T lymphocytes and umbilical vein endothelial cells were used to assay the in vitro activity of RX-111. Mouse and rat models of disease were used to assay the anti-inflammatory activity of RX-111 in vivo. Circular dichroism and UV/Vis absorption spectroscopy were used to study the binding of RX-111 to the glycosaminoglycan, heparin. T lymphocyte rolling on endothelial cells under shear flow was used to assay RX-111 activity in vitro. Delayed-type hypersensitivity (DTH) and tri-nitrobenzene sulfonic acid (TNBS)-induced colitis in mice and experimental autoimmune encephalomyelitis (EAE) in rats were used to assay anti-inflammatory activity of RX-111 in vivo. RX-111 was shown to bind directly to heparin. It inhibited leukocyte rolling on endothelial cells under shear flow and reduced inflammation in the mouse model of DTH. RX-111 was efficacious in the mouse model of inflammatory bowel disease, TNBS-induced colitis and the rat model of multiple scl...Continue Reading

References

Apr 1, 1976·The Journal of Experimental Medicine·R N CahillZ Trnka
Jan 1, 1989·Arteriosclerosis : an Official Journal of the American Heart Association, Inc·A D Cardin, H J Weintraub
Dec 1, 1985·Journal of Neuroimmunology·C FeurerS Cammisuli
Apr 5, 1996·Science·E C Butcher, L J Picker
Nov 1, 1996·The Journal of Clinical Investigation·B K ReuterJ L Wallace
Feb 7, 1998·The Journal of Experimental Medicine·R A WarnockU H von Andrian
Sep 19, 1998·Journal of the Neurological Sciences·J J ArchelosH P Hartung
Jun 11, 1999·Advances in Immunology·E C ButcherM Briskin
Aug 7, 2002·The American Journal of Pathology·Jutta RenkonenRisto Renkonen
Dec 12, 2003·Nature Reviews. Immunology·Ulrich H von Andrian, Thorsten R Mempel
Mar 23, 2004·Annual Review of Immunology·Steven D Rosen
Feb 9, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jesús Rivera-NievesKlaus Ley
Mar 15, 2005·American Journal of Respiratory and Critical Care Medicine·Sanna K Toppila-SalmiRisto L O Renkonen
Sep 8, 2006·The FEBS Journal·Markus Sperandio
Dec 5, 2006·Biological & Pharmaceutical Bulletin·Hiroto Kawashima
Nov 20, 2009·Clinical and Experimental Immunology·K ManganoF Nicoletti
Jan 20, 2010·Lancet Neurology·Joseph R Berger, Sidney A Houff
Oct 12, 2010·The Journal of Biological Chemistry·Jotaro HirakawaHiroto Kawashima
Mar 5, 2011·British Journal of Pharmacology·Cris S ConstantinescuBruno Gran
Oct 6, 2011·Nature Reviews. Gastroenterology & Hepatology·Kirstin M Taylor, Peter M Irving
Jan 1, 2007·Profiles of Drug Substances, Excipients, and Related Methodology·Richard J Prankerd
Sep 29, 2012·Nature Reviews. Immunology·Jean-Philippe GirardReinhold Förster
Jan 12, 2013·Science·Ira Tabas, Christopher K Glass
Jun 5, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Koichiro TsuboiHiroto Kawashima

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