title: Small-molecule inhibitors of the TLR3/dsRNA complex.
abstract: The protein-RNA interface has been regarded as "undruggable" despite its importance in many biological processes. The toll-like receptor 3 (TLR3)/double-stranded RNA (dsRNA) complex provides an exciting target for a number of infectious diseases and cancers. We describe the development of a series of small-molecule probes that were shown to be competitive inhibitors of dsRNA binding to TLR3 with high affinity and specificity. In a multitude of assays, compound 4a was profiled as a potent antagonist to TLR3 signaling and also repressed the expression of downstream signaling pathways mediated by the TLR3/dsRNA complex, including TNF-α and IL-1β.
authors.affiliation: Department of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, Colorado 80309, United States.
authors.forename: Kui
authors.initials: K
authors.lastname: Cheng
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.forename: Hang
authors.initials: H
authors.lastname: Yin
mesh_terms: D000818:Animals; D002460:Cell Line; D051379:Mice; D008958:Models, Molecular; D012330:RNA, Double-Stranded / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D051196:Toll-Like Receptor 3 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D012330:RNA, Double-Stranded; D051196:Toll-Like Receptor 3