WZ4-49-8

WZ4-49-8 is a small molecule pyrazolopyrimidine derivative that acts as a selective inhibitor of the c-Fes (Feline sarcoma oncogene) tyrosine kinase. Developed through a collaboration between the Dana-Farber Cancer Institute and the University of Pittsburgh, WZ4-49-8 was utilized as a chemical probe to investigate the role of c-Fes in the proliferation of Acute Myelogenous Leukemia (AML) cells, particularly those harboring Flt3 mutations. Preclinical data indicates that WZ4-49-8 possesses approximately 20-fold greater selectivity for c-Fes over wild-type Flt3 in vitro. In cell-based assays using MV4-11 AML cells, it demonstrated growth-suppressive activity with an IC50 of 1.86 μM, though it was found to be less potent than dual Flt3/c-Fes inhibitors, highlighting the potential requirement for multi-kinase inhibition in treating Flt3-driven leukemias.