Antagonists

Both nucleotide-based and small-molecule antagonists of TLR9 are known, and due to the similarity in receptor and ligand structures are generally effective against both TLR9 and TLR7. Inhibitory oligo-nucleotide sequences are typically guanine-rich competitive antagonists that bind receptor without causing activation [90]. Two series of small-molecule inhibitors have been described. The first series, exemplified by compound 27, was optimized on the substituted quinoline structure of chloroquine and has nanomolar potency in a CpG oligo-stimulated viability assay [91,92], and in a transfected TLR9 reporter assay [93]. A more recently described series of diamino-substituted phenylbenzoxazoles (28-30) also show nanomolar potency in cell-based assays [94,95].

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