IRAK-1-4 Inhibitor I

IRAK-1-4 Inhibitor I is an inhibitor of interleukin-1 receptor-associated kinase 1/4 (IRAK 1/4) with IC₅₀s of 0.2 μM and 0.3 μM, respectively. IC50 & Target: IC50: 0.2 μM (IRAK-4), 0.3 μM (IRAK-1)^[1] In Vitro: IRAK-1-4 Inhibitor I has IC₅₀ greater than the highest concentration tested (10 μM) against a panel of 27 other kinases, including the most closely homologous (outside of the IRAK family) Lck and pp60^SRC. Additionally, IRAK-1-4 Inhibitor I does not show any signs of cytotoxicity in a 72 h proliferation assay in HeLa cells (ED₅₀>30 μM). Significant inhibition of IRAK-1 is observed with IRAK-1-4 Inhibitor I (IRAK-1 IC₅₀=0.3 μM)^[1]. IRAK-1/4 inhibitor eliminates the LPS-induced increases in Bcl10, NF-κB, and IL-8. IRAK-1/4 mediates LPS-induced IL-8 activation and functions upstream of Bcl10. The LPS-induced increase in Bcl10 declines by 73% (from 5.18±0.22 to 2.36±0.08 ng/mL), and the IL-8 response decline by 60% (from 2.64±0.31 to 1.14±0.08 ng/mL)^[2].