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Application of compound MG 132 in preparation of medicine for treating leucocythemia

A technology of MG-132 and a compound is applied in the application field of compound MG-132 in the preparation of leukemia drugs, and can solve the problems of different effects, treatment failure, cell apoptosis and the like

Inactive Publication Date: 2006-08-30
GUANGZHOU INST OF BIOMEDICINE & HEALTH CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The treatment of AML M2 is currently based on chemotherapy such as cytarabine and daunorubicin. Although the remission rate is high, it is easy to relapse and cause treatment failure. The median survival time is less than 2 years, and the 5-year survival rate is less than 40%.
MG-132 can reduce the degradation of proteins bound to ubiquitin in mammalian cells, resulting in the accumulation of a large number of proteins that should be cleared in cells and causing apoptosis. Currently, it is mainly used in laboratory research and has not been used in clinical practice. report
In view of the fact that different tumors have different pathogenesis, proteasome also has different components or subunits, and compounds have different effects on different subunits in different tumors, can MG-132 be used as a drug to treat human leukemia, especially acute myeloid leukemia and chronic myelogenous leukemia have not been reported

Method used

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  • Application of compound MG 132 in preparation of medicine for treating leucocythemia
  • Application of compound MG 132 in preparation of medicine for treating leucocythemia
  • Application of compound MG 132 in preparation of medicine for treating leucocythemia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Example 1: Degradation effect of MG-132 on AML1-ETO fusion protein.

[0034] Kasumi-1 cells were treated with different concentrations of MG-132. After 24 hours of treatment, the cells were collected and lysed with 1× cell lysate to extract proteins, and then Western blot was performed with anti-ETO antibody (purchased from Santa Cruz, USA). It was found that MG-132 could regulate the expression of AML1-ETO fusion protein, partially degrade the AML1-ETO protein and produce degradation bands. After Kasumi-1 cells were treated with MG-132 at a concentration of 500nM for 24 hours, the expression of AML1-ETO fusion protein changed and was obviously degraded. see figure 1 , where ΔAML1-ETO is the fragment formed after degradation of AML1-ETO

Embodiment 2

[0036] With different concentrations (1×10 -9 ~1×10 -5 M) MG-132 treated cell line Kasumi-1 cells containing t(8; 21) chromosomal translocation and CML cell line K562 cells containing t(9; 22) chromosomal translocation, added 2-( 2-Methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfonic acid phenyl)-2H-tetrazole monosodium salt (WST-8) CCK-8 detection reagent, and then incubated for 4 hours, then use a microplate reader to measure the absorbance of the two at 450nm (OD 450 ). It was found that MG-132 treatment could significantly reduce the OD of Kasumi-1 cells and K562 cells 450 , indicating that MG-132 can significantly inhibit the proliferation of Kasumi-1 cells and K562 cells, and the inhibition rate is positively correlated with the drug concentration, see figure 2 , image 3 .

[0037] According to the growth inhibitory effect of MG-132 on Kasumi-1 cells, the half inhibitory concentration (IC) of MG-132 to Kasumi-1 cells was calculated 50 ) is (3.77±1.49)×10 ...

Embodiment 3

[0040] With different concentrations (1×10 -9 ~1×10 -6 M) MG-132 treated the cell line Kasumi-1 cells containing t(8; 21) chromosomal translocation and the CML cell line K562 cells containing t(9; 22) chromosomal translocation respectively, after 12, 24, At 36 and 48 hours, the number of living cells was counted by the fetal hope blue exclusion method and the growth curves of Kasumi-1 cells and K562 cells were drawn. It was found that MG-132 could significantly inhibit the growth of Kasumi-1 cells and K562 cells, and this effect showed a time- For dose dependence, see Figure 4 and Figure 5 .

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Abstract

An application of the compound MG-132 in preparing the medicines for treating the leukemia including M2-type acute medullary leukemia and chronic granulocytic leukemia is disclosed. Its advantages are low dosage and moderate cost.

Description

technical field [0001] The present invention relates to the application of compound MG-132 in the preparation of medicines for treating leukemia, in particular to the application of MG-132 in the preparation and treatment of acute myeloid leukemia (AML M2) and chronic myeloid leukemia with t(8;21) chromosome translocation. Drug application in chronic myeloid leukemia (CML). Background technique [0002] Leukemia is a group of hematopoietic stem / progenitor cell diseases with abnormal genome, which can be divided into acute and chronic leukemia. According to the different cell series, acute patients are divided into acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), and the latter is divided into several subtypes M0-M7; chronic leukemia is divided into chronic myeloid leukemia (chronic myeloid leukemia). leukemia, CML) and chronic lymphocytic leukemia. [0003] The incidence of AML M2 is higher, accounting for 25% of all AML, of which 40%-80% have t (8; 21)...

Claims

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Application Information

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IPC IPC(8): A61K38/55A61P35/02A61K31/704A61K38/19
Inventor 周光飚张凤香冯亦教
Owner GUANGZHOU INST OF BIOMEDICINE & HEALTH CHINESE ACAD OF SCI
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