Novel application of chiauranib in preparation of medicines for treating acute myeloid leukemia

A technology for acute myeloid and leukemia, applied in drug combinations, antineoplastic drugs, active ingredients of heterocyclic compounds, etc., to achieve the effect of reducing treatment-related complications, small side effects, and good safety

Active Publication Date: 2019-06-21
THE FIRST AFFILIATED HOSPITAL OF XIAMEN UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Preliminary studies have shown that it has a lethal effect on a variety of solid tumors, including non-small cell lung cancer, liver cancer, colon cancer, and lymph

Method used

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  • Novel application of chiauranib in preparation of medicines for treating acute myeloid leukemia
  • Novel application of chiauranib in preparation of medicines for treating acute myeloid leukemia
  • Novel application of chiauranib in preparation of medicines for treating acute myeloid leukemia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] Example 1 Research on the effect of cioroni on the inhibition of AML cell proliferation

[0045] Take 2×10 5 AML cell lines in the logarithmic growth phase (including HL60, K562, Molm13, NB4, Thp1, U937, MV411, OCI-AML3) were inoculated in 24-well plates, and the control group and different concentrations of Theoloni groups (0.5, 1 , 2, 4, 8, 16μM) after 48h and 72h, the CCK8 kit was used to detect the proliferation of AML cells in different experimental groups, and the results were as follows figure 1 And as shown in Table 1, the details are as follows:

[0046] Table 1 The IC50 values ​​of the inhibitory effect on the proliferation of various AML cell lines after 48h and 72h of treatment with cioroni respectively

[0047]

[0048] from figure 1 (A)- figure 1 (B) It can be seen that with the increase of the concentration of cioroni, the survival rate of AML cells decreased significantly. From the results of 48h and 72h, it can be seen that the survival rate of A...

Embodiment 2

[0049] It can be seen from Table 1 that Cioronib inhibited the proliferation of various AML cells after acting for 48h and 72h, and the IC50 value at 72h was lower than the IC50 value at 48h. Example 2 The effect of Ciolonib on inhibiting AML cell proliferation was further verified by colony formation unit (CFU)

[0050] In the present example, the inhibition of AML cell proliferation by Ciolonib was verified, and the specific steps were as follows:

[0051] 1) Take 2×10 5 The Molm13 cells in the logarithmic growth phase were seeded in 24-well plates, and the control group and the Theoroni group (2, 4 μM) were set to act for 24 hours;

[0052] 2) 500 Molm3 cells from the control group and the Theoloni group (2, 4 μM) were inoculated in methylcellulose culture at 37°C and 5% CO 2 After 10 days of culture in a humidity incubator, the number of colony units was counted with an inverted microscope. All cultures were carried out in 6-well plates (3 wells were replanted), and mor...

Embodiment 3

[0055] Example 3 Using Annexin V / PI double-staining method to detect the apoptosis of AML cells induced by cioroni

[0056] Take 2×10 5 AML cell lines in the logarithmic growth phase (including HL60, K562, Molm13, NB4, Thp1, U937, MV411, OCI-AML3) were inoculated in 24-well plates, and the control group and the different concentrations of Theoloni groups (1, 2 , 4, 8μM) after 48h and 72h, the Annexin V / PI kit was used to detect the apoptosis of AML cells in different experimental groups, and the results were as follows image 3 shown.

[0057] from image 3 (A)- image 3 (B) It can be seen that Cioronib has different degrees of apoptosis-inducing effects on various AML cell lines in a time- and concentration-dependent manner.

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Abstract

The invention relates to the field of application of medicines, in particular to novel application of chiauranib in preparation of medicines for treating acute myeloid leukemia. The novel applicationis application of chiauranib or pharmaceutically acceptable salts, esters and solvates thereof in preparation of medicines for preventing and/or treating acute myeloid leukemia. Chiauranib inhibits growth and induces apoptosis and colony formation of acute myeloid leukemia cells through Src/Fyn/p38 and Erk/MEK signaling pathways.

Description

technical field [0001] The invention relates to the field of drug application, in particular to the new use of cioroni in the preparation of medicines for treating acute myeloid leukemia. Background technique [0002] Acute myeloid leukemia (AML) is a malignant clonal proliferative disease of hematopoietic stem and progenitor cells, which is highly heterogeneous, and is characterized by blocked differentiation of leukemia cells and massive proliferation of primitive cells, resulting in anemia, platelet Reduction, infection, tissue and organ infiltration and other related clinical symptoms, the current main treatment for AML is combined chemotherapy and allogeneic hematopoietic stem cell transplantation (Short NJ, Rytting ME, Cortes JE, Acute myeloidleukaemia. [J]. Lancet 2018 08 18; 392 (10147)) (Short NJ, Rytting ME, Cortes JE, Acute myeloid leukaemia. [J]. Lancet 2018 08 18; 392(10147)). [0003] In recent years, with the improvement of the dose of multi-drug combination ...

Claims

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Application Information

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IPC IPC(8): A61K31/47A61P35/02
Inventor 徐兵邓漫漫鲁先平查洁赵海军李志峰付鑫
Owner THE FIRST AFFILIATED HOSPITAL OF XIAMEN UNIV
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