This technology includes a class of 3-(pyridin-2-yl)imidazo[1,2-a]pyridines that acts as a dual inhibitor of Flt3 and IRAK for the treatment of cancer. Acute myeloid leukemia (AML) remains associated with poor outcomes despite advances in our understanding of the complicated molecular events driving leukemogenesis and malignant progression. Those patients harboring mutations in the FLT3 receptor tyrosine kinase have a particularly poor prognosis; however, treatment targeting FLT3 mutations has failed to achieve robust and sustained clinical responses. We have recently identified the secondary adaptor kinase IRAK as being one key element of this resistance. In parallel, we found that a class of 3-(pyridin-2- yl)imidazo[1,2-a]pyridines has dual activity versus Flt3 and IRAK kinases and a superior anticancer profile relative to Flt3-only inhibitors.
Further clinical work could establish a dual inhibitor of Flt3 and IRAK for the treatment of cancer, including acute myeloid leukemia (AML).
The dual-targeting of both Flt3 and IRAK appears to provide a superior anti-cancer outcome.