WZ4-49-1

WZ4-49-1 is a small molecule pyrazolopyrimidine that functions as a selective inhibitor of the Fes (Feline Sarcoma) protein tyrosine kinase. It was developed as a chemical probe to study the role of Fes in hematopoietic signaling and malignancy. In the context of acute myelogenous leukemia (AML), WZ4-49-1 has been shown to inhibit the growth and induce apoptosis of cells harboring Flt3 internal tandem duplication (ITD) mutations, where Fes acts as a critical downstream signaling mediator. While it displays some activity against Flt3, it is significantly more potent against Fes, making it a valuable tool for dissecting Fes-dependent pathways in myeloid leukemia. It acts as an ATP-competitive inhibitor, blocking the kinase activity of Fes and potentially offering therapeutic benefit in Flt3-ITD+ AML cases where Fes is overexpressed and constitutively active.