IRAK-1-4 Inhibitor I is an inhibitor of both IRAK-1 and IRAK-4 with IC50 values of 0.3μM and 0.2μM , respectively [1].
IL-1 receptor-associated kinases play important roles in signal transduction. There are totally four members of the IRAKs, they are IRAK-1, IRAK-2, IRAK-M and IRAK-4. IRAK-4 can activate NF-κB and MAPK pathways and it is shown that the inhibition of IRAK-4 can be an anti-inflammatory therapy. IRAK-1-4 Inhibitor I is an analog of an Initial IRAK-4 inhibitor hit, which is screened out from a small molecule li brary against IRAK-4. With the less basic N-ethylenemorpholine moiety, IRAK-1-4 Inhibitor I has a higher potency than other analogs. Additionally, it does not show any cytotoxicity in a 72 h proliferation assay in HeLa cells(ED50 >30μM) [1].
References:
[1] Jay P. Powers, Shyun Li, Juan C. Jaen, Jinqian Liu, Nigel P. C. Walker, Zhulun Wang and Holger Wesche. Discovery and initial SAR of inhibitors of interleukin-1 receptor-associated kinase-4. Bioorganic & Medicinal Chemistry Letters. 2006, 16: 2842–2845.