Characterization of a Small Molecule IRAK4 Inhibitor for the Treatment of Inflammatory Disorders and Hematologic Malignancies

摘要

Recent advances in genome sequencing and tumor proteome and transcriptome analysis uncovered a key role for MyD88-dependent Toll-Like Receptor (TLR) and Interleukin-1 Receptor (IL-1R)-mediated signaling pathways in multiple hematologic malignancies. In myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML), overexpression of TLR pathway components is associated with deregulation of innate immune system and subsequent induction of pro inflammatory environment in the bone marrow. IRAK4 is a key protein kinase in all MyD88-dependent signaling pathways, potentially making it an ideal target for hematologic malignancies.