Detailed introduction to the working principle and biological activity of Quizartinib

Quizartinib is a new type of small molecule tyrosine kinase inhibitor (TKI), mainly used to treat patients with acute myeloid leukemia (AML) carrying FLT3-ITD mutations. FLT3 (FMS-like tyrosine kinase3) is a receptor type expressed in hematopoietic stem cells Tyrosine kinase, mutated FLT3especially ITD (internal tandem repeat) mutations can lead to sustained activation of the receptor, thereby promoting excessive proliferation of leukemia cells and evading apoptosis. Quizartinib highly selectively inhibits FLT3 kinase activity and blocks its signal transduction, thereby inducing tumor cell death and controlling disease progression.

In terms of target selection, Quizartinib is significantly more selective for FLT3 than other kinases, especially showing strong biological activity against FLT3-ITD mutant cells. Both in vitro and in vivo studies have shown that quizartinib can rapidly reduce the proliferation ability of FLT3-ITD positive leukemia cells and induce their apoptosis. In addition, its inhibitory effect on wild-type FLT3 is relatively weak, which means that it has less inhibitory effect on normal hematopoietic cells, which is beneficial to reducing side effects such as bone marrow suppression, reflecting good targeting and therapeutic window.

From the perspective of pharmacokinetics and biological activity, quizartinib has a long half-life (about more than 24 hours), supports once-daily oral administration, and has good bioavailability. In clinical trials, such as the QuANTUM-R study, quizartinib monotherapy has been shown to significantly prolong FLT3-ITDmutations The overall survival (OS) and event-free survival (EFS) of AML patients are particularly significant in relapsed or refractory populations. The results of this study provide important evidence for the positioning of quizartinib in the treatment of AML and led to its approval in many countries.

However, quizartinib also has certain medication risks, especially in ECGQTSafety concerns regarding interval prolongation require close monitoring of electrolyte levels and cardiac function in clinical use. In addition, because some FLT3 mutation subtypes (such as D835 point mutations) are resistant to quizartinib, clinical use may need to be combined with other drugs to improve efficacy. Overall, as a highly selective FLT3 inhibitor, quizartinib has clear mechanism advantages and biological activity basis in the field of AML targeted therapy, providing a new precision treatment for patients with FLT3-ITD mutations.

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