The Research Team Led by Prof. Wei Ge Made New Progress in the Development of Targeted Therapy Drugs for Acute Myeloid Leukemia


About one third of patients with acute myeloid leukemia (AML) are caused by mutations in FLT3 tyrosine kinases and the patients of Internal Tandem Duplication (ITD) mutation have very poor prognosis. Currently, R&D of FLT3-targeted drugs for FLT3-mutated AML has became one of the hot research topics.

In April 2017, the research team led by Wei Ge from the Institute of Basic Medical Sciences and National Laboratory of Medical Molecular Biology published an article titled MZH29 is A Novel Potent Inhibitor that Overcomes Drug Resistance-FLT3 Mutations in Acute Myeloid Leukemia (IF=12.1) ( on the Leukemia, a well-known professional journal of blood disease. By a series of in vitro screening experiments, the authors found that the compound MZH29 had a therapeutic effect on FLT3-mutated AML, especially for such mutations as FLT3-D835H/Y/V, FLT3-K663Q, and FLT3-ITD-F691L. The possible mechanism via which MZH29 exerts its effect on drug-resistant mutation was preliminarily confirmed by computer molecular simulation and proteomic experiments. Meanwhile, the authors validated the in vivo activity and toxicity of the drugs in the mouse tumor models. The research has proved that MZH29 is a potential candidate drug for FLT3-mutated AML and thus brings new hope for patients with this maligancy.


The research was led by the research team of Prof. Wei Ge. The first author of this paper is doctoral candidate Benhong Xu from the team and the corresponding author is Prof. Wei Ge. This research is supported by CAMS Innovation Fund for Medical Sciences (2016-I2M-1-003), PUMC Youth Fund (3332015020), and NN-CAMS Union Talent Fund.



Figure descriptions:


Figure a: In vivo suppression of MZH29 on the signal pathway of FLT3 phosphorylation at different times;

Figure b:  MZH29 significantly inhibits the growth of subcutaneous tumor in mouse model ;

Figures c and d: MZH29 significantly prolonged the survive time of mouse model.




(Institute of Basic Medical Sciences)