The mechanism of action of giritinib (segatan) and its targeting principle for FLT3 mutations

Gilteritinib (Gilteritinib) is an oral small molecule tyrosine kinase inhibitor (TKI), mainly used to treat acute myeloid leukemia (AML) associated with FLT3 mutations. Its core mechanism of action is to selectively inhibit the activity of FLT3 tyrosine kinase, thereby blocking abnormal signaling pathways and inhibiting the proliferation and survival of leukemia cells. Unlike traditional chemotherapy, giritinib can target specific mutation targets of leukemia cells to achieve precise treatment.

FLT3mutations are common in AML patients, including internal tandem repeat (ITD) mutations and tyrosine kinase domain (TKD) point mutations. These mutations can lead to continued activation of the FLT3 receptor and promote abnormal proliferation of leukemia cells. Giritinib binds to the FLT3 mutant receptor, inhibits its autophosphorylation and downstream signal transduction, and blocks the growth and division of malignant cells, thereby achieving disease control.

Giritinib is highly selective for FLT3-ITD and TKD mutations. It can target abnormal cells while relatively reducing the impact on normal hematopoietic cells. This specificity not only improves the therapeutic effect, but also reduces the risk of systemic toxic side effects, making it easier for patients to tolerate it during long-term medication, and improving treatment safety and quality of life.

In clinical application, giritinib can be used as a single agent or in combination with chemotherapy for patients with relapsed or refractory AML. By precisely inhibiting the FLT3 mutation signaling pathway, giritinib can delay disease progression, improve the remission rate, and provide personalized targeted treatment options for FLT3positive AML patients, significantly improve patient prognosis, and provide an important choice for clinical treatment.

Reference materials:https://www.drugs.com/