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10.1038/nchembio.2518 http://scihub22266oqcxt.onion/10.1038/nchembio.2518 C5726935!5726935!29155428     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Nat+Chem+Biol 2018 ; 14 (1): 58-64 Nephropedia Template TP {{tp|p=29155428|t=2018. Small-molecule inhibition of TLR8 through stabilization of its resting state |pdf=|usr=}}{{29155428}} gab.com Text Small-molecule inhibition of TLR8 through stabilization of its resting state JO: Nat Chem Biol http://www.kidney.de/pget.php?&tw=1&pmid=29155428 #FOAvip Endosomal Toll-like receptors (TLR3/7/8/9) are highly analogous sensors for various viral or bacterial RNA/DNA molecular patterns. Nonetheless, few small-molecules can selectively modulate these TLRs. In this manuscript, we identified the first human TLR8-specific small-molecule antagonists via a novel inhibition mechanism. Crystal structures of two distinct TLR8-ligand complexes validated a unique binding site on the protein-protein interface of the TLR8 homodimer. Upon binding to this new site, the small-molecule ligands stabilize the preformed TLR8 dimer in its resting state, preventing activation. As a proof of concept of their therapeutic potential, we have demonstrated that these drug-like inhibitors are able to suppress TLR8-mediated proinflammatory signaling in various cell lines, human primary cells, and patient specimens. These results not only suggest a novel strategy for TLR inhibitor design, but also shed critical mechanistic insight into these clinically important immune receptors. Twit Text FOAVip Small-molecule inhibition of TLR8 through stabilization of its resting state ????Nat Chem Biol http://www.kidney.de/pget.php?&tw=1&pmid=29155428 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29155428 #FOAvip English Wikipedia <ref>{{Cite pmid|29155428}}</ref> Small-molecule inhibition of TLR8 through stabilization of its resting state #MMPMID29155428 Zhang S; Hu Z; Tanji H; Jiang S; Das N; Li J; Sakaniwa K; Jin J; Bian Y; Ohto U; Shimizu T; Yin H Nat Chem Biol 2018[Jan]; 14 (1): 58-64 PMID29155428show ga Endosomal Toll-like receptors (TLR3/7/8/9) are highly analogous sensors for various viral or bacterial RNA/DNA molecular patterns. Nonetheless, few small-molecules can selectively modulate these TLRs. In this manuscript, we identified the first human TLR8-specific small-molecule antagonists via a novel inhibition mechanism. Crystal structures of two distinct TLR8-ligand complexes validated a unique binding site on the protein-protein interface of the TLR8 homodimer. Upon binding to this new site, the small-molecule ligands stabilize the preformed TLR8 dimer in its resting state, preventing activation. As a proof of concept of their therapeutic potential, we have demonstrated that these drug-like inhibitors are able to suppress TLR8-mediated proinflammatory signaling in various cell lines, human primary cells, and patient specimens. These results not only suggest a novel strategy for TLR inhibitor design, but also shed critical mechanistic insight into these clinically important immune receptors. äSmall-molecule inhibition of TLR8 through stabilization of its resting(epmc).pdf DeepDyve Pubget Overpricing