IRAK inhibitor 4 is an inhibitor of interleukin-1 receptor-associated kinase 4 (IRAK4).

IRAK1/4, at a concentration of 20 μM, suppresses LPS-induced IL-6 production but does not affect p38 phosphorylation in alveolar macrophages (AMs). Concurrently, the use of both IRAK1/4 and Rip2 inhibitors significantly reduces TLR2-mediated cytokine production in sarcoidosis patient-derived peripheral blood mononuclear cells (PBMCs) and AMs. Moreover, IRAK4 is found to be both overexpressed and activated in T-cell acute lymphoblastic leukemia (T-ALL), with IRAK4 mRNA levels being higher in T-ALL cells from patients compared to those in thymic T cells or peripheral blood T cells. Additionally, the absence of IRAK-4 compromises the ability of macrophages and dendritic cells (DCs) to produce pro-inflammatory mediators in response to M. bovis and M. tuberculosis. IRAK-4-deficient cells, when stimulated with E. coli LPS, show significantly slower activation kinetics across all signaling proteins examined and a marked decrease in p65 phosphorylation.

IRAK-4-/- mice demonstrate an elevated bacterial load across all organs at 15, 30, and 60 days post-infection. Moreover, MCL1, unlike BCL-xL, negates the therapeutic benefits of combined IRAK1/4 inhibitor and ABT-737 treatment in vivo. Additionally, these mice experience significantly decreased survival rates after aerosol infection compared to their IRAK-4+/+ or IRAK-4+/- counterparts.