tailieunhanh - Báo cáo khoa học: Novel synthetic gluco-disaccharide RSCL-0409 – a lipopolysaccharide-induced Toll-like receptor-mediated signalling antagonist

The regulation of cytokines and pro-inflammatory genes is an absolute essentiality to combat inflammatory diseases. The present study investigated the effects of 4-O-chloroacetyl-2,3-di-O-acetyl-6-O-levulinoyl-b-d-glucopyr-anosyl]-(1-3)-1-O-(p-methoxyphenyl)-2-deoxy-2-N-trichloroacetyl-4,6-O-ben-zylidene-a-d-glucopyranoside (RSCL-0409), a novel small molecule Toll-like receptor (TLR) signalling antagonist, and its mechanism of action in human monocytic (THP-1) cells stimulated with lipopolysaccharide (LPS) | Novel synthetic gluco-disaccharide RSCL-0409 -a lipopolysaccharide-induced Toll-like receptor-mediated signalling antagonist o n I n lốo 1111 t i 1 p I a I riatl a2 Ạ lzọh owo Rpl Io ft 1 l h a Is nrliit Racha1 A Ọ li A o ft ĩ RKĩỉrmĩỉ1 IVI al 11 LA ixa Iiui I I lai Icci L atia Mxoiiaya Deidiy 1X1 laiaiiviei LJdsid Aoiivvaiii wiiaiiiia Anuradha Sharma1 Shiva Singh1 Shakti Upadhyay2 and Vikram Rajagopal1 1 Drug Discovery and Development Group Reliance Life Sciences Pvt. Ltd Navi Mumbai India 2 EID Parry India Ltd Chennai India Keywords inflammation lipopolysaccharide monocytes NF-kB TLR signalling tumour necrosis factor-a Correspondence V. Rajagopal Drug Discovery and Development Group Reliance Life Sciences Pvt. Ltd Dhirubhai Ambani Life Sciences Center Rabale Navi Mumbai-400701 India Fax 91 22 67678099 Tel 91 22 67678854 E-mail vikram_rajagopal@ These authors contributed equally to this work Received 9 December 2009 revised 16 January 2010 accepted 21 January 2010 doi The regulation of cytokines and pro-inflammatory genes is an absolute essentiality to combat inflammatory diseases. The present study investigated the effects of 4-ơ-chloroacetyl-2 3-di-ơ-acetyl-6-ơ-levulinoyl-P-D-glucopyr-anosyl - 1-3 -1-ơ- p-methoxyphenyl -2-deoxy-2-N-trichloroacetyl-4 6-ơ-ben-zylidene-a-D-glucopyranoside RSCL-0409 a novel small molecule Toll-like receptor TLR signalling antagonist and its mechanism of action in human monocytic THP-1 cells stimulated with lipopolysaccharide LPS . In THP-1 and cells RSCL-0409 suppressed LPS-induced production of tumour necrosis factor-a TNF-a with a 50 inhibitory concentration of pM and mRNA expression of ICAM-1 Cox-2 and interleukin-8 with no evidence of cytotoxicity. RSCL-0409 also suppressed TNF-a production from LPS-stimulated human peripheral blood mononuclear cells. Similar results were obtained in vivo in a murine model of LPS-induced inflammation where pretreatment with RSCL-0409 .