IRAK inhibitor 1

1042224-63-4

C17H19N5

DMSO : 12.2 mg/mL (41.59 mM; Need ultrasonic and warming)

Immunology/Inflammation; Protein Tyrosine Kinase/RTK

IRAK inhibitor 1 is a potent IRAK-4 inhibitor with IC₅₀ of 216 nM, is poorly active against JNK-1 and JNK-2 with IC₅₀ of 3.801 uM, and >10 uM, respectively. IC50 & Target: IC50: 216 nM (IRAK-4), 3.801 uM (JNK-1), >10 uM (JNK-2)^[1] In Vitro: IRAK inhibitor 1 possesses significant potency in an IRAK-4 enzyme assay but is poorly active against JNK-1 and JNK-2^[1]. IRAK-4 is a novel member of the IRAK family with unique functional properties. IRAK-4 is the closest human homolog to Pelle. Endogenous IRAK-4 interacts with IRAK-1 and TRAF6 in an IL-1-dependent manner, and overexpression of IRAK-4 can activate NF-kappaB as well as mitogen-activated protein (MAP) kinase pathways. Most strikingly, and in contrast to the other IRAKs, IRAK-4 depends on its kinase activity to activate NF-kappaB. In addition, IRAK-4 is able to phosphorylate IRAK-1, and overexpression of dominant-negative IRAK-4 is blocking the IL-1-induced activation and modification of IRAK-1, suggesting a role of IRAK-4 as a central element in the early signal transduction of Toll/IL-1 receptors, upstream of IRAK-1. IRAK-4 shares the domain structure of the other IRAKs and it is able to activate similar signal transduction pathways, namely NF-kappaB and MAPK pathways. It rapidly and transiently associates with IRAK-1 and TRAF6 in an IL-1-dependent manner but it is not functionally redundant with IRAK-1. IRAK-4 is an active protein kinase and requires its kinase activity to activate NF-kappaB. IRAK-4 might act upstream of IRAK-1 as an IRAK-1 activator^[2].