C29 is a novel inhibitor of TLR2/1 and TLR2/6 signaling induced by synthetic and bacterial TLR2 agonists in human HEK-TLR2 and THP-1 cells, but only TLR2/1 signaling in murine macrophages.

C29 blunts hTLR2/1 and hTLR2/6 signaling in HEK-TLR2 Stable transfectants and THP-1 Cells. C29 blocks P3C- and P2C-induced IL-8 mRNA dose-dependently in HEK-TLR2 stable transfectants. C29 also inhibits P3C- and P2C-induced IL-1β gene expression significantly at both 1 h and 4 h following stimulation, as well as both P3C- and P2C-induced NF-κB–luciferase activity in transiently transfected HEK293T cells expressing hTLR2 and an NF-κB–sensitive luciferase reporter construct. C29 preferentially inhibits TLR2/1 signaling in primary murine macrophages. C29 blocks TLR2 bacterial agonist-induced proinflammatory gene expression in HEK-TLR2 Cells and murine macrophages. C29 inhibits ligand-induced interaction of TLR2 with MyD88 and blocks MAPK and NF-κB activation[1].

C29L inhibits TLR2/1-induced inflammation in mice. Mice treated twice with C29L before administration of P3C significantly blocks IL-12 p40 and TNF-α liver cytokine mRNA and serum protein. C29L has a significant inhibitory effect at the later time point for IL-12 p40[1].