FLT3 / Aurora kinase A and B

Class

Small molecule dual kinase inhibitor

Pathway

FLT3 signal transduction and mitotic Aurora kinase pathway; active in quizartinib-resistant FLT3-ITD AML models

FLT3 is a receptor tyrosine kinase found on immature blood-forming cells; when a segment of the gene is duplicated (an internal tandem duplication, or ITD), the receptor becomes constitutively active and drives uncontrolled proliferation, a common and aggressive genetic subtype of acute myeloid leukemia (AML). Aurora kinases A and B are separate enzymes that control mitosis, the process by which cells divide, regulating events such as spindle formation and chromosome separation. Inhibiting FLT3 alone can suppress the driving oncogenic signal, but leukemic clones frequently develop secondary mutations that restore receptor activity and blunt drug effect. Pairing FLT3 inhibition with Aurora kinase inhibition provides a second, independent way to stop leukemic cells from dividing, since Aurora kinase activity is required for mitosis regardless of FLT3 mutation status. This dual mechanism aims to produce deeper and more durable suppression of leukemic proliferation than either target alone, and to remain active even against leukemic clones that have adapted to escape single-agent FLT3 blockade. This approach is relevant broadly to relapsed or treatment-resistant AML, where clonal evolution under selective drug pressure is a central clinical challenge.