Analyze the types of diseases that Quizartinib can treat

Quizartinib (Quizartinib) is a highly selective FLT3 receptor tyrosine kinase inhibitor that effectively treats acute myeloid leukemia (AML) by inhibiting the activity of FLT3 mutations. FLT3 receptor, as a tyrosine kinase receptor, is widely expressed on hematopoietic stem cells and their precursor cells, and is involved in cell proliferation and survival. Under normal physiological conditions, FLT3 receptor activates downstream signaling pathways by binding to its ligand, promoting the proliferation, differentiation and survival of blood cells. However, FLT3 gene mutations, especially internal tandem duplication (ITD) mutations, lead to sustained activation of the FLT3 receptor, causing excessive proliferation of leukemia cells and providing the basis for the progression and drug resistance of AML.

Quizatinib inhibits the kinase activity of the FLT3 receptor by competing with the ATP binding site of theFLT3 receptor. Activation of the FLT3 receptor is completed through a phosphorylation reaction, and by preventing this process, quizartinib directly inhibits the downstream transmission of FLT3 signals. This inhibitory effect not only effectively slows down the proliferation of leukemia cells, but also promotes the death of diseased cells by inducing apoptosis.

In the treatment ofAML, quizartinib not only acts on the FLT3 receptor itself, but also enhances the therapeutic effect by affecting other molecules related to the FLT3 signaling pathway. Sustained activation of the FLT3 receptor is often accompanied by the activation of other cell survival pathways, such as the PI3K/Akt pathway. The activation of these pathways provides leukemia cells with the conditions to survive and escape treatment. Quizartinib further enhances its anti-leukemia effect by simultaneously inhibiting the abnormal activation of these signaling pathways.

Another major feature of quizartinib is its inhibitory effect on different mutant subtypes ofFLT3 gene. In addition to ITD mutations, other variants such as point mutations and exon 12 mutations of FLT3 can also be effectively inhibited by quizartinib. This broad-spectrum inhibitory effect gives quizatinib therapeutic potential in patients with different types of FLT3 mutation-positive AML.

References：https://www.medicines.org.uk/emc/product/15557/smpc