NCGC-1481

NCGC-1481 is a small molecule type I inhibitor of FMS-like tyrosine kinase 3 (FLT3), developed by the National Center for Advancing Translational Sciences (NCATS). It is primarily utilized in the study of acute myeloid leukemia (AML) to target FLT3 mutations, including internal tandem duplication (ITD) and the gatekeeper mutation F691L. As a type I inhibitor, it binds to the active conformation of the FLT3 kinase, effectively suppressing downstream STAT5 signaling. Research indicates that NCGC-1481 can be used to investigate resistance mechanisms, such as the kinase-independent activation of the MAPK pathway via Grb2 in FLT3-F691L mutant cells.