Interleukin-1 receptor-associated kinases (IRAKs) are important mediators in the signal transduction of Toll/IL-1 receptor (TIR) family members. Dysregulation of TIR signaling, typified by increased NF-κB activity, results in the development of some cancers and other diseases, making the development of IRAK inhibitors a potential therapeutic strategy. IRAK-1/4 inhibitor is a benzimidazole that disrupts the activity of IRAK-1 and -4 with IC50 values of 0.3 and 0.2 μM, respectively. It demonstrates IC50 values >10 μM in a panel of 27 other kinases tested. This compound has been used to inhibit a pro-inflammatory response in microglia isolated from clinically diagnosed Alzheimer’s disease patients.
