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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
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SYSNO ASEP 0461932 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název 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 Tvůrce(i) Harris, N. (IL)
Koppel, J. (SK)
Zsila, F. (HU)
Juhás, Štefan (UZFG-Y) RID, ORCID
Ilková, G. (SK)
Kogan, F. Y. (IL)
Lahmy, O. (IL)
Wildbaum, G. (IL)
Karin, N. (IL)
Zhuk, R. (IL)
Gregor, P. (IL)Zdroj.dok. Inflammation Research - ISSN 1023-3830
Roč. 65, č. 4 (2016), s. 285-294Poč.str. 10 s. Forma vydání Tištěná - P Jazyk dok. eng - angličtina Země vyd. CH - Švýcarsko Klíč. slova small molecule drug ; glycosaminoglycan ; heparin binding protein ; heparan sulfate ; inflammation ; autoimmune disease Vědní obor RIV EB - Genetika a molekulární biologie Institucionální podpora UZFG-Y - RVO:67985904 UT WOS 000372288200004 EID SCOPUS 84961061068 DOI 10.1007/s00011-016-0915-4 Anotace 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 sclerosis, EAE.
RX-111 exercises its broad spectrum anti-inflammatory activity by a singular mechanism of action, inhibition of protein binding to the cell surface GAG, heparan sulfate. RX-111 and related thieno[2,3-c]pyridine derivatives are potential therapeutics for the treatment of inflammatory and autoimmune diseases.Pracoviště Ústav živočišné fyziologie a genetiky Kontakt Jana Zásmětová, knihovna@iapg.cas.cz, Tel.: 315 639 554 Rok sběru 2017
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