What is the mechanism of action of Quizartinib?

Quizartinib is an innovative treatment drug for patients with acute myeloid leukemia (AML) who are positive for FLT3 internal tandem duplication (ITD) mutations. It is a small molecule inhibitor of the receptor tyrosine kinase FLT3. It exerts its unique therapeutic effect by binding with high affinity to the adenosine triphosphate (ATP) binding domain of FLT3.

Specifically, quizartiniband its major active metaboliteAC886 showed 10-fold lower affinity for the FLT3-ITD mutation than for FLT3 in binding assays. This selective binding inhibits FLT3 kinase activity, thereby preventing receptor autophosphorylation. FLT3 kinase plays a key role in AML, and its abnormal activation is often closely related to disease progression and poor prognosis. Quizartinibby inhibiting the activity of FLT3 kinase, effectively blocks downstream FLT3 receptor signaling, thereby blocking FLT3-ITD-dependent cell proliferation.

This mechanism of action enables Quizartinib to specifically target FLT3-ITD mutated AML cells and reduce damage to normal cells. Clinical trials have proven that quizartinib performs well in the treatment of FLT3-ITD-positive AML patients and can significantly extend the progression-free survival and overall survival of patients. In addition, quizartinib can also improve patients' clinical symptoms, such as fatigue, fever, anemia, etc., and reduce patients' pain, thereby improving patients' quality of life.

Of note, quizartinib is often used in combination with standard cytarabine and anthracycline induction therapy and cytarabine consolidation therapy as maintenance monotherapy after consolidation chemotherapy. This combination of drugs can further enhance the therapeutic effect and bring better prognosis to patients. However, when using quizartinib, you also need to pay attention to its possible side effects, such as cardiotoxic reactions such as QT interval prolongation, as well as gastrointestinal discomforts such as nausea, vomiting, and diarrhea. Therefore, it is necessary to closely monitor the patient's physical condition during medication and adjust the treatment plan as needed.

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Reference: https://go.drugbank.com/drugs/DB12874