Cell-based screening scheme used to identify selective NOD2 inhibitors.

<p>The compound collection was screened for inhibitors of MDP-induced IL-8 secretion in 293/hNOD2 stable cells. Active inhibitors were then tested for selectivity against IL-8 induced by alternative pathways including NOD1, TNFR1 and TLR2 as well as for direct inhibitors of RIP2 kinase. The activity of selective NOD2 inhibitors was then confirmed in cells expressing NOD2 endogenously and against agonist-independent NOD2 signaling.</p>