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10.1177/0961203315591031 http://scihub22266oqcxt.onion/10.1177/0961203315591031 C4616909!4616909 !26085597     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26085597 &cmd=llinks): Failed to open stream: HTTP request failed! 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Drug-like analogues of the parasitic worm-derived immunomodulator ES-62 are therapeutic in the MRL/Lpr model of systemic lupus erythematosus |pdf=|usr=}}{{26085597 }} gab.com Text Drug-like analogues of the parasitic worm-derived immunomodulator ES-62 are therapeutic in the MRL/Lpr model of systemic lupus erythematosus JO: Lupus http://www.kidney.de/pget.php?&tw=1&pmid=26085597 #FOAvip INTRODUCTION: ES-62, a phosphorylcholine (PC)-containing immunomodulator secreted by the parasitic worm Acanthocheilonema viteae, protects against nephritis in the MRL/Lpr mouse model of systemic lupus erythematosus (SLE). However, ES-62 is not suitable for development as a therapy and thus we have designed drug-like small molecule analogues (SMAs) based around its active PC-moiety. To provide proof of concept that ES-62-based SMAs exhibit therapeutic potential in SLE, we have investigated the capacity of two SMAs to protect against nephritis when administered to MRL/Lpr mice after onset of kidney damage. METHODS: SMAs 11a and 12b were evaluated for their ability to suppress antinuclear antibody (ANA) generation and consequent kidney pathology in MRL/Lpr mice when administered after the onset of proteinuria. RESULTS: SMAs 11a and 12b suppressed development of ANA and proteinuria. Protection reflected downregulation of MyD88 expression by kidney cells and this was associated with reduced production of IL-6, a cytokine that exhibits promise as a therapeutic target for this condition. CONCLUSIONS: SMAs 11a and 12b provide proof of principle that synthetic compounds based on the safe immunomodulatory mechanisms of parasitic worms can exhibit therapeutic potential as a novel class of drugs for SLE, a disease for which current therapies remain inadequate. Twit Text FOAVip Drug-like analogues of the parasitic worm-derived immunomodulator ES-62 are therapeutic in the MRL/Lpr model of systemic lupus erythematosus ????Lupus http://www.kidney.de/pget.php?&tw=1&pmid=26085597 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26085597 #FOAvip English Wikipedia <ref>{{Cite pmid|26085597 }}</ref> Drug-like analogues of the parasitic worm-derived immunomodulator ES-62 are therapeutic in the MRL/Lpr model of systemic lupus erythematosus #MMPMID26085597 Rodgers DT ; Pineda MA ; Suckling CJ ; Harnett W ; Harnett MM Lupus 2015[Nov]; 24 (13 ): 1437-42 PMID26085597 show ga INTRODUCTION: ES-62, a phosphorylcholine (PC)-containing immunomodulator secreted by the parasitic worm Acanthocheilonema viteae, protects against nephritis in the MRL/Lpr mouse model of systemic lupus erythematosus (SLE). However, ES-62 is not suitable for development as a therapy and thus we have designed drug-like small molecule analogues (SMAs) based around its active PC-moiety. To provide proof of concept that ES-62-based SMAs exhibit therapeutic potential in SLE, we have investigated the capacity of two SMAs to protect against nephritis when administered to MRL/Lpr mice after onset of kidney damage. METHODS: SMAs 11a and 12b were evaluated for their ability to suppress antinuclear antibody (ANA) generation and consequent kidney pathology in MRL/Lpr mice when administered after the onset of proteinuria. RESULTS: SMAs 11a and 12b suppressed development of ANA and proteinuria. Protection reflected downregulation of MyD88 expression by kidney cells and this was associated with reduced production of IL-6, a cytokine that exhibits promise as a therapeutic target for this condition. CONCLUSIONS: SMAs 11a and 12b provide proof of principle that synthetic compounds based on the safe immunomodulatory mechanisms of parasitic worms can exhibit therapeutic potential as a novel class of drugs for SLE, a disease for which current therapies remain inadequate. |*Mice, Inbred MRL lpr [MESH] |Adjuvants, Immunologic/pharmacology [MESH] |Animals [MESH] |Antibodies, Antinuclear/metabolism [MESH] |Cytokines/metabolism [MESH] |Disease Models, Animal [MESH] |Female [MESH] |Helminth Proteins/*pharmacology [MESH] |Immunologic Factors [MESH] |Interleukin-6/metabolism [MESH] |Lupus Erythematosus, Systemic/drug therapy/metabolism/pathology [MESH] |Mice [MESH] |Myeloid Differentiation Factor 88/genetics [MESH] |Nephritis/drug therapy/pathology [MESH]Drug-like analogues of the parasitic worm-derived immunomodulator ES-6(epmc).pdf DeepDyve Pubget Overpricing