{"id":106,"date":"2018-04-01T22:10:02","date_gmt":"2018-04-01T21:10:02","guid":{"rendered":"https:\/\/admin.innaxon.com\/?p=106"},"modified":"2021-11-25T18:24:00","modified_gmt":"2021-11-25T18:24:00","slug":"a-novel-small-molecule-tlr4-antagonist-iaxo-102-2015","status":"publish","type":"post","link":"https:\/\/admin.innaxon.com\/index.php\/2018\/04\/01\/a-novel-small-molecule-tlr4-antagonist-iaxo-102-2015\/","title":{"rendered":"2015 A novel small molecule TLR4 antagonist (IAXO-102)…"},"content":{"rendered":"
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A novel small molecule TLR4 antagonist (IAXO-102) negatively regulates non-hematopoietic toll like receptor 4 signalling and inhibits aortic aneurysms development<\/strong>\u00a0(2015)<\/span><\/strong><\/h2>\n<\/div>\n<\/div>\n
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Atherosclerosis. 242:563 (2015)<\/strong><\/h3>\n

Huggins C1, Pearce S1, Peri F2, Neumann F3, Cockerill G1, Pirianov G4.<\/p>\n

1<\/strong>\u00a0Institute of Cardiovascular Sciences and Cell Biology, St Georges University of London, UK
\n2<\/strong>\u00a0Department of Biotechnology and Biosciences, University of Milano-Bicocca, Italy.
\n3<\/strong>\u00a0Innaxon, Tewkesbury, UK.
\n4<\/strong>\u00a0Department of Biomedical and Forensic Sciences, Anglia Ruskin University, Cambridge, UK. Electronic address: grisha.pirianov@anglia.ac.uk.<\/p>\n


\nObjectives<\/strong><\/h3>\n

The toll-like receptors (TLRs), including TLR4, have been shown to play a crucial role in vascular inflammatory diseases, such as atherosclerosis and aneurysm. The main goal of this study was to determine the potential of IAXO-102 (Innaxon, Tewkesbury), a novel small molecule TLR4 antagonist, to modulate non-hematopoietic TLR4 proinflammatory signalling and inhibit experimental abdominal aortic aneurysm (AAA) development.<\/p>\n


\nMethods<\/strong><\/h3>\n

Human umbilical vein endothelial cells (HUVEC) and Angiotensin II-induced experimental AAA development were our in\u00a0vitro and in\u00a0vivo models respectively. Western blotting, antibody array and ELISA approaches were used to explore the effect of IAXO-102 on TLR4 functional activity on two levels: modulation of TLR4-induced mitogen activated protein kinases (MAPK) and p65 NF-kB phosphorylation and expression of TLR4 dependent proinflammatory proteins.<\/p>\n


\nResults<\/strong><\/h3>\n

Following activation of TLR4, in\u00a0vitro\/in\u00a0vivo data revealed that IAXO-102 inhibited MAPK and p65 NF-kB phosphorylation associated with down regulation of the expression of TLR4 and TLR4 dependent proinflammatory proteins. Furthermore, IAXO-102 decreased Angiotensin II-induced aortic expansion, rupture and incidence of AAA.<\/p>\n


\nConclusions<\/strong><\/h3>\n

These results demonstrate the ability of IAXO-102 to negatively regulate TLR4 signalling and to inhibit experimental AAA development, suggesting the potential therapeutic use of this TLR4 antagonist for pharmacological intervention of AAA.<\/p>\n<\/div>\n<\/div>\n<\/article>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

A novel small molecule TLR4 antagonist (IAXO-102) negatively regulates non-hematopoietic toll like receptor 4 signalling and inhibits aortic aneurysms development\u00a0(2015) Atherosclerosis. 242:563 (2015) Huggins C1, Pearce S1, Peri F2, Neumann F3, Cockerill G1, Pirianov G4. 1\u00a0Institute of Cardiovascular Sciences and Cell Biology, St Georges University of London, UK 2\u00a0Department of<\/p>\n

Read More<\/a><\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[5],"tags":[8,15,13,12,14,11],"class_list":["post-106","post","type-post","status-publish","format-standard","hentry","category-literature","tag-antagonist","tag-aortic-aneurysms","tag-iaxo","tag-iaxo-102","tag-non-hematopoietic","tag-tlr4"],"yoast_head":"\n2015 A novel small molecule TLR4 antagonist (IAXO-102)... - Innaxon Therapeutics<\/title>\n<meta name=\"description\" content=\"The main goal of this study was to determine the potential of IAXO-102 (Innaxon, Tewkesbury), a novel small molecule TLR4 antagonist, to modulate non-hematopoietic TLR4 proinflammatory signalling and inhibit experimental abdominal aortic aneurysm (AAA) development.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/admin.innaxon.com\/index.php\/2018\/04\/01\/a-novel-small-molecule-tlr4-antagonist-iaxo-102-2015\/\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"2015 A novel small molecule TLR4 antagonist (IAXO-102)... - 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