AST-487 is an inhibitor of RET (IC50 = 0.88 uM), FLT3 (Ki = 0.52 uM), KDR (IC50 = 0.17 uM), c-Abl (IC50 = 0.02 uM), and c-Kit (IC50 = 0.5 uM). AST-487 has potent and selective antiproliferative effects 7 on primary AML patient cells and cell lines expressing FLT3-ITD or FLT3 kinase domain point mutants. AST-487, which selectively targets mutant FLT3 protein kinase activity, is also shown to override PKC412 resistance in vitro, and has significant antileukemic activity in an in vivo model of FLT3-ITD(+) leukemia. Finally, the combination of NVP-AST487 with standard chemotherapeutic agents leads to enhanced inhibition of proliferation of mutant FLT3-expressing cells. AST-487 displays high selectivity and potency toward FLT3 as a molecular target, and could potentially be used to override drug resistance in AML.