HH-IA-208

HH-IA-208 is a novel chalcone derivative that acts as a dual inhibitor of Fms-like tyrosine kinase 3 (FLT3) and microtubule polymerization. Identified through cell-based screenings, it demonstrates potent activity against leukemia cell lines expressing FLT3 internal tandem duplications (FLT3-ITD), a common mutation in acute myeloid leukemia (AML) associated with poor prognosis. HH-IA-208 inhibits FLT3 signaling and disrupts tubulin polymerization, leading to mitotic arrest and apoptotic cell death. Notably, it has shown the ability to overcome acquired resistance mediated by FLT3 tyrosine kinase domain (TKD) mutations, such as D835Y, making it a promising lead for the treatment of resistant AML.