This technology includes a series of imidazo[1,2-a]pyridines with potent inhibition of FLT3, which retains potent binding and activity against FLT3 tyrosine kinase domain and gatekeeper mutations. This chemotype exhibits superior anti-leukemic activity against the common clinically-relevant FLT3-mutant acute myeloid leukemia (AML) in vitro and in vivo. Tyrosine kinase domain mutations are a common cause of acquired resistance to FLT3 inhibitors used to treat FLT3-mutant AML. This invention builds upon an earlier IP position with new analogs.
If successful in human clinical trials, these agents could be used to treat a variety of hematological diseases, including but not limited to AML, myelodysplastic syndrome, diffuse large B-cell lymphoma, and other blood cancers.
These agents have activity versus mutations in the acquired resistance space and versus non-IRAK inhibitors in the adaptive resistance space, and our lead agents have better activity relative to all existing FLT3 inhibitors in relevant FLT3 models.