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J Am Chem Soc. 2011 Mar 23;133(11):3764-7. doi: 10.1021/ja111312h. Epub 2011 Feb 28.

Small-molecule inhibitors of the TLR3/dsRNA complex.

Author information

1
Department of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, Colorado 80309, United States.

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.

PMID:
21355588
PMCID:
PMC3068529
DOI:
10.1021/ja111312h
[Indexed for MEDLINE]
Free PMC Article

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