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-? and IL-1?.

SUBMITTER: Cheng K 

PROVIDER: S-EPMC3068529 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature