NOD1 is a member of the NACHT and leucine-rich repeat domain-containing proteins (NLR) family of innate immunity proteins. It recognizes distinct molecular patterns from bacterial ligands and activates NF-κB, stress kinases, and interferon response factors important for host defense and inflammation. Hereditary polymorphisms in the NOD1 gene are associated with asthma, inflammatory bowel disease, multiple sclerosis, and other disorders. Noditinib-1 selectively inhibits NOD1-dependent activation of NF-κB and MAPK signaling (IC50 = 0.6 μM) and also inhibits NOD1-induced IL-8 production in MCF-7 cells without affecting viability. In ex vivo dendritic cell culture, 15 μM noditinib-1 reduced cell-surface expression of CD83, CD86, and HLA-DR and inhibited expression of IL-1β, IL-6, and TNF-α. The mechanism of this inhibitor’s activity is thought to involve alteration of the subcellular targeting of NOD1.
