Small-Molecule Inhibitors of the TLR3/dsRNA Complex
Year: 2011
Type: article
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.
DOI: 10.1021/ja111312h
Authors: Kui Cheng, Xiaohui Wang, Hang Yin
Institution: University of Colorado Boulder
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Awards: G1114177658, Transforming Clinical Pain Control by Targeting a Novel Non-Neuronal Receptor, Probing Opioid-Induced Glial Activation with Peptide Antagonists, G3801284106, Optimizing the Clinical Efficacy of Opioids by TLR4 Blockade, G5925976606, G6410635432, Developing Small-Molecule Probes for Opioid-Induced Glial Activation, G7855982944, Colorado Clinical and Translational Science Institute (UL1)
OpenAlex ID: W2002075586