How Gilteritinib works

Gilitinib is a potent and selective inhibitor of two mutations in the internal tandem duplication (ITD) and tyrosine kinase domain (TKD) of the FLT3 receptor. Similarly, giritinibalso inhibitsAXL and ALK tyrosine kinases. FLT3 and AXL are molecules involved in cancer cell growth. The activity of geritinib allows inhibition of the phosphorylation of FLT3 and its downstream targets such as STAT5, ERK and AKT. Interest in the FLT3 transmembrane tyrosine kinase increased when studies reported that approximately 30% of acute myeloid leukemia patients develop mutationally activated isoforms. Likewise, mutated ITD is associated with poor patient prognosis, while mutated TKD confer resistance mechanisms to FLT3 tyrosine kinase inhibitors and AXL tyrosine kinase tends to confer resistance mechanisms to chemotherapy.