35754-32-6Relevant academic research and scientific papers
Rationally Designed Small-Molecule Inhibitors Targeting an Unconventional Pocket on the TLR8 Protein-Protein Interface
Jiang, Shuangshuang,Tanji, Hiromi,Yin, Kejun,Zhang, Shuting,Sakaniwa, Kentaro,Huang, Jian,Yang, Yi,Li, Jing,Ohto, Umeharu,Shimizu, Toshiyuki,Yin, Hang
, p. 4117 - 4132 (2020/05/22)
Rational designs of small-molecule inhibitors targeting protein-protein interfaces have met little success. Herein, we have designed a series of triazole derivatives with a novel scaffold to specifically intervene with the interaction of TLR8 homomerization. In multiple assays, TH1027 was identified as a highly potent and specific inhibitor of TLR8. A successful solution of the X-ray crystal structure of TLR8 in complex with TH1027 provided an in-depth mechanistic insight into its binding mode, validating that TH1027 was located between two TLR8 monomers and recognized as an unconventional pocket, thereby preventing TLR8 from activation. Further biological evaluations showed that TH1027 dose-dependently suppressed the TLR8-mediated inflammatory responses in both human monocyte cell lines, peripheral blood mononuclear cells, and rheumatoid arthritis patient specimens, suggesting a strong therapeutic potential against autoimmune diseases.
TRIAZOLE COMPOUNDS AS ANTIVIRALS
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Paragraph 0168, (2014/01/18)
The present invention discloses compounds of Formula I: wherein the variables in Formula I are defined as described herein. Also disclosed are pharmaceutical compositions containing such compounds and methods for using the compounds of Formula I in the prevention or treatment of HCV infection.
