GSK669 inhibits NOD2 but not NOD1 mediated responses.

<p>(A) Structure of GSK669, the original hit identified from the NOD2 HTS screening cascade. (B) Concentration response curves showing GSK669 selectively inhibits MDP-stimulated IL-8. IL-8 secretion in either MDP treated 293/hNOD2 or iE-DAP treated 293/hNOD1 stable cell lines was measured in the presence of increasing concentrations of GSK669. Data are mean ± SD from 6 independent assays. (C) Selective inhibition of NOD2-mediated MAPK phosphorylation by GSK669. Serum-starved 293/hNOD1 or NOD2 stable cells were pre-incubated with compound at the concentrations indicated and then stimulated for 1 hour with either Tri-DAP or MDP, respectively. Phospho-p38, JNK and ERK1/2 were identified in cell lysates by western blotting. A RIP2 inhibitor compound was used as a positive control. Similar results were obtained in 5 (293/hNOD2) and 2 (293/hNOD1) separate experiments.</p>