Background:

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]

Reference:
[1]. Morris, M.C., Gilliam, E.A., and Li, L. Innate immune programing by endotoxin and its pathological consequences. Front.Immunol. 5, 1-8 (2015).
[2]. Neal, M.D., Jia, H., Eyer, B., et al. Discovery and validation of a new class of small molecule toll-like receptor 4 (TLR4) inhibitors. PLoS One 8(6), e65779 (2013).
[3]. Wipf, P., Eyer, B.R., Yamaguchi, Y., et al. Synthesis of anti-inflammatory α-and β-linked acetamidopyranosides as inhibitors of toll-like receptor 4 (TLR4). Tetrahedron Letters 56(23), 3097-3100 (2015).