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Toll-like receptor 4 (TLR4) is activated by lipopolysaccharide (LPS), with LPS-binding protein, to initiate an innate immune response, which typically includes increased expression of TNFα.[1] TLR4-C34 is a 2-acetamidopyranoside that inhibits TLR4 signaling in enterocytes and macrophages in vitro when used at 10 μM.[2],[3] It does not affect signaling through either TLR2 or TLR9. TLR4-C34, used at 1 mg/kg in vivo, also reduces systemic inflammation in mouse models of endotoxemia and necrotizing enterocolitis.[2] It markedly decreases the basal expression of TNFα, as well as LPS-induced iNOS and TNFα expression, in intestinal tissue isolated from patients with necrotizing enterocolitis.[2]

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