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10.1021/acschembio.7b01060 http://scihub22266oqcxt.onion/10.1021/acschembio.7b01060 C5996755!5996755 !29553248     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=29553248 &cmd=llinks): Failed to open stream: HTTP request failed! 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A High Content Screen in Macrophages Identifies Small Molecule Modulators of STING-IRF3 and NFkB Signaling |pdf=|usr=}}{{29553248 }} gab.com Text A High Content Screen in Macrophages Identifies Small Molecule Modulators of STING-IRF3 and NFkB Signaling JO: ACS Chem Biol http://www.kidney.de/pget.php?&tw=1&pmid=29553248 #FOAvip We screened a library of bioactive small molecules for activators and inhibitors of innate immune signaling through IRF3 and NFkB pathways with the goals of advancing pathway understanding and discovering probes for immunology research. We used high content screening to measure the translocation from the cytoplasm to nucleus of IRF3 and NFkB in primary human macrophages; these transcription factors play a critical role in the activation of STING and other pro-inflammatory pathways. Our pathway activator screen yielded a diverse set of hits that promoted nuclear translocation of IRF3 and/or NFkB, but the majority of these compounds did not cause activation of downstream pathways. Screening for antagonists of the STING pathway yielded multiple kinase inhibitors, some of which inhibit kinases not previously known to regulate the activity of this pathway. Structure-activity relationships (SARs) and subsequent chemical proteomics experiments suggested that MAPKAPK5 (PRAK) is a kinase that regulates IRF3 translocation in human macrophages. Our work establishes a high content screening approach for measuring pro-inflammatory pathways in human macrophages and identifies novel ways to inhibit such pathways; among the targets of the screen are several molecules that may merit further development as anti-inflammatory drugs. Twit Text FOAVip A High Content Screen in Macrophages Identifies Small Molecule Modulators of STING-IRF3 and NFkB Signaling ????ACS Chem Biol http://www.kidney.de/pget.php?&tw=1&pmid=29553248 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29553248 #FOAvip English Wikipedia <ref>{{Cite pmid|29553248 }}</ref> A High Content Screen in Macrophages Identifies Small Molecule Modulators of STING-IRF3 and NFkB Signaling #MMPMID29553248 Koch PD ; Miller HR ; Yu G ; Tallarico JA ; Sorger PK ; Wang Y ; Feng Y ; Thomas JR ; Ross NT ; Mitchison T ACS Chem Biol 2018[Apr]; 13 (4 ): 1066-1081 PMID29553248 show ga We screened a library of bioactive small molecules for activators and inhibitors of innate immune signaling through IRF3 and NFkB pathways with the goals of advancing pathway understanding and discovering probes for immunology research. We used high content screening to measure the translocation from the cytoplasm to nucleus of IRF3 and NFkB in primary human macrophages; these transcription factors play a critical role in the activation of STING and other pro-inflammatory pathways. Our pathway activator screen yielded a diverse set of hits that promoted nuclear translocation of IRF3 and/or NFkB, but the majority of these compounds did not cause activation of downstream pathways. Screening for antagonists of the STING pathway yielded multiple kinase inhibitors, some of which inhibit kinases not previously known to regulate the activity of this pathway. Structure-activity relationships (SARs) and subsequent chemical proteomics experiments suggested that MAPKAPK5 (PRAK) is a kinase that regulates IRF3 translocation in human macrophages. Our work establishes a high content screening approach for measuring pro-inflammatory pathways in human macrophages and identifies novel ways to inhibit such pathways; among the targets of the screen are several molecules that may merit further development as anti-inflammatory drugs. |Active Transport, Cell Nucleus/drug effects [MESH] |Drug Evaluation, Preclinical [MESH] |Humans [MESH] |Interferon Regulatory Factor-3/*antagonists & inhibitors [MESH] |Intracellular Signaling Peptides and Proteins/physiology [MESH] |Macrophages/*chemistry [MESH] |Membrane Proteins/*antagonists & inhibitors [MESH] |NF-kappa B/*metabolism [MESH] |Protein Kinase Inhibitors/pharmacology [MESH] |Protein Serine-Threonine Kinases/physiology [MESH] |Signal Transduction/drug effects [MESH]A High Content Screen in Macrophages Identifies Small Molecule Modulat(epmc).pdf DeepDyve Pubget Overpricing