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Updated: Oct 23, 2025

Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling
Published on: July 26, 2017
Synthesis, structure-activity relationship studies and evaluation of a TLR 3/8/9 agonist and its analogues
Anindya Sarkar1, Anushka C Galasiti Kankanamalage1, Qian Zhang2
1Department of Chemistry and Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA.
Abstract:
A comprehensive SAR study of a putative TLR 3/8/9 agonist was conducted. Despite the excitement surrounding the potential of the first small molecule TLR3 agonist with a compound that additionally displayed agonist activity for TLR8 and TLR9, compound 1 displayed disappointing activity in our hands, failing to match the potency (EC50) reported and displaying only a low efficacy for the extent of stimulated NF-κB activation and release. The evaluation of >75 analogs of 1, many of which constitute minor modifications in the structure, failed to identify any that displayed significant activity and none that exceeded the modest activity found for 1.
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