Small-Molecule Inhibitors of the TLR3/dsRNA Complex
- 28 February 2011
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 133 (11), 3764-3767
- https://doi.org/10.1021/ja111312h
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.Keywords
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