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Latest Research Discoveries | Hang YIN publishes"Small-molecule inhibition of TLR8 through stabilization of its resting state" in Nature Chemical Biology
Endosomal Toll-like receptors (TLR3, TLR7, TLR8, and TLR9) are highly analogous sensors for various viral or bacterial RNA and 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.
About Us
A Letter from the Dean
Mission
At a Glance
History
Organization
Advisory Board
Faculty
Tenure Track
Teaching
Experimental Techniques
Research
Research
Research Overview
Areas of Research
Academics
Undergraduate
Graduate
Postdoctoral
Alumni
International Exchange
Core Facilities
About Center of Pharmaceutical Technology
Connect
Overview
Partnerships
Giving
Contact us