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Application of chelidonine in preparation of medicine for treating acute myelogenous leukemia with FLT3-ITD mutation

A technology of FLT3-ITD and chelidonine, which can be used in drug combinations, pharmaceutical formulations, anti-tumor drugs, etc., can solve problems such as no research on the effect of chelidonine, and achieve the effects of reducing infiltration, prolonging survival time, and increasing expression.

Active Publication Date: 2022-05-13
FUDAN UNIV SHANGHAI CANCER CENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are currently no studies investigating the role of Chelidonine in AML with FLT3-ITD mutations

Method used

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  • Application of chelidonine in preparation of medicine for treating acute myelogenous leukemia with FLT3-ITD mutation
  • Application of chelidonine in preparation of medicine for treating acute myelogenous leukemia with FLT3-ITD mutation
  • Application of chelidonine in preparation of medicine for treating acute myelogenous leukemia with FLT3-ITD mutation

Examples

Experimental program
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Effect test

Embodiment 1

[0041] Embodiment 1: in vitro experiment

[0042] 1. Chelidonine inhibits the proliferation of FLT3-ITD mutant cell lines

[0043] In order to determine the effect of Chelidonine on the proliferation of cells with FLT3-ITD mutation, we selected the MV4;11 cell line with FLT3-ITD mutation as the research object, and also used two cell lines without FLT3-ITD, K562 and Kasumi-1 as comparison. Eight groups of different concentrations of Chelidonine were used to treat the above three cell lines, and CCK-8 was used to detect cell proliferation. The results are shown in figure 1 .

[0044] According to the test results of CCK-8, the concentration of Chelidonine ≤ 1 μM will not affect the proliferation of cells. However, the concentration of Chelidonine ≥ 2.5 μM can significantly inhibit the proliferation of FLT3-ITD mutant MV4; 11 cell line, and its 24h IC50 is 2.8 μM. The 24h IC50 of the two cell lines without FLT3-related mutations were: K562 4.9μM, Kasumi-1 5.8μM. It is sugge...

Embodiment 2

[0048] Embodiment 2: experiment in vivo

[0049] In the in vivo experiment, the MV4;11 CDX mouse model was constructed, and the number of cells injected into the tail vein of NSG mice d0 was 1×10 6 , The experiment was divided into 4 groups. Experimental group 1 was the Chelidonine treatment group, 7 animals in each group, and the survival time was observed and recorded; Experimental group 2 was the non-medication group, 7 animals in each group, and the survival time was observed and recorded; Experimental group 3 was Chelidonine drug treatment group. Treatment group, experimental group 4 is the non-medication group, and these two groups are the regular execution group. The incidence and tumor burden were measured after sacrifice to determine the therapeutic effect of Chelidonine in vivo. The earliest onset time of the established NSG mouse CDX model was d16 after transplantation, and the body weight decreased by 9% in 24 hours. Of the 6 NSG mice in the Chelidonine treatment...

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Abstract

The invention relates to the field of new application of medicines, in particular to application of a small molecule compound Chelidonine in preparation of a medicine for treating acute myelogenous leukemia (AML) with FLT3-ITD mutation. In the invention, chelidonine is used for inhibiting MV4 of FLT3-ITD mutation in vitro; 11 cell proliferation and apoptosis induction can be realized, and the FLT3-ITD mutant AML can be targeted to act on FLT3-ITD mutant AML. In in-vivo experiments, the polypeptide can reduce the proportion of bone marrow hCD45 + cells, reduce the infiltration of bone marrow and spleen, increase the expression of liver and spleen apoptosis protein Caspase3 and prolong the survival time of NSG mice, has an in-vivo anti-tumor effect, can be used as a new means for FLT3-ITD mutated AML drug intervention, and brings a new hope to treatment of FLT3-ITD mutated AML.

Description

technical field [0001] The invention relates to the technical field of new application of medicines, in particular, the application of the small molecular compound chelidonine (Chelidonine) in the preparation of medicines for treating acute myeloid leukemia with FLT3-ITD mutation. Background technique [0002] Acute leukemia is one of the hematological malignancies that seriously threaten human health, and acute myeloid leukemia (AML) is the most common type of adult leukemia, accounting for about 70%. However, the long-term survival rate of AML patients under 60 years old is only 35%-40%, and the long-term survival rate of AML patients over 60 years old drops to 5-15%. For elderly AML patients who cannot tolerate intensive chemotherapy, the median survival time is only 5-10 months. [0003] FLT3 mutations in AML patients mainly include internal tandem duplication (ITD) mutations and tyrosine kinase domain (tyrosine kinase domain, TKD) point mutations. FLT3-ITD mutation is...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4741A61P35/02
CPCA61K31/4741A61P35/02
Inventor 王鹏王虹
Owner FUDAN UNIV SHANGHAI CANCER CENT
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