Page 12 - F. Cell biology

[F. Cell biology-6]

Anticancer effect of an IRAK4 inhibitor on ABC-DLBCL cells

Su Bin Sin¹, Young Sik Cho¹˙*

¹College of Pharmacy, Keimyung University, Daegu 42601, Republic of Korea

Potent interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitors have been emerging as a blockade of toll-like

receptor/ I interleukin-l receptor (TLR/ILR) signaling pathway to treat autoimmune-related diseases such as

rheumatoid arthritis and multiple sclerosis. Additionally, some cancers have been reported to show an increase in
IRAK4 activity or to bear L265P mutation in MyD88, an intracellular adaptor protein of TLR/ILlR, resulting in
constitutive activation of a cascade of downstream signaling pathway. A hit compound 6-(imidazo 1, 2-a] pyridine-

3-yl)-N-(4-piperidinyl)-2-pyridinamine was initially discovered as a JNK kinase inhibitor, but was later found to have
considerable potency in an in vitro enzymatic assay with IC50 of 216 nM. To delineate the underlying mechanism

of IRAK4 target-based inhibition of lymphoma proliferation, this compound was further evaluated in cell-based
assays. An IRAK4 inhibitor potently down-regulated not only the LPS-induced NFκB transcriptional activity in NFκB-

luciferase A549 cell line, but also NO production in LPS-stimulated RAW264.7.