IRAK-1-4 Inhibitor I

509093-47-4

C20H21N5O4

DMSO : 14.29 mg/mL (36.14 mM; Need ultrasonic)

Immunology/Inflammation; Protein Tyrosine Kinase/RTK

IRAK-1-4 Inhibitor I is a dual inhibitor of IRAK4 and IRAK1 with IC₅₀ of 0.2 uM and 0.3 uM, respectively. IC50 & Target: IC50: 0.2 uM (IRAK-4), 0.3 uM (IRAK-1)^[1] In Vitro: IRAK-1-4 Inhibitor I has IC₅₀ greater than the highest concentration tested (10 uM) 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 uM). Significant inhibition of IRAK-1 is observed with IRAK-1-4 Inhibitor I (IRAK-1 IC₅₀=0.3 uM)^[1]. IRAK-1/4 inhibitor eliminates the LPS-induced increases in Bcl10, NF-kappaB, 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].