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Application of compound PSI in preparation of medicine for treating leucocythemia

A compound, leukemia technology, applied in drug combinations, anti-tumor drugs, pharmaceutical formulations, etc., can solve the problems of treatment failure, easy recurrence, and median survival time of less than 2 years

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, daunorubicin / dunorubicin. Although the remission rate is high, it is easy to relapse and cause treatment failure. The median survival time is less than 2 years. The annual survival rate is less than 40%
In view of the fact that different tumors have different pathogenesis, proteasome also has different components or subunits, and proteasome inhibitors have different effects on different subunits in different tumors. Can the compound PSI be used as a drug to treat human leukemia, especially acute myeloid leukemia? leukemia and chronic myelogenous leukemia, which have not been reported yet

Method used

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  • Application of compound PSI in preparation of medicine for treating leucocythemia
  • Application of compound PSI in preparation of medicine for treating leucocythemia
  • Application of compound PSI in preparation of medicine for treating leucocythemia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Example 1: Degradation effect of PSI on AML1-ETO fusion protein.

[0033] Kasumi-1 cells were treated with different concentrations of PSI, and after 24 hours of treatment, the cells were collected and lysed with 1× cell lysate to extract protein, and then Western blot was performed with anti-ETO antibody (purchased from Santa Cruz, USA). The results showed that PSI could regulate the expression of AML1-ETO fusion protein, degrade part of AML1-ETO protein and produce degradation bands. (See figure 1 , the left is the control, and the right is the change of AML1-ETO fusion protein after being treated with 50nM concentration of PSI for 24 hours. )

Embodiment 2

[0035] With different concentrations of 1×10 -9 ~1×10 -5 The PSI of M 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, and added 2-(2-formazan) after 44 hours CCK- 8 detection reagents, and then incubated for 4 hours, and then measured the absorbance (OD 450 ). It was found that PSI treatment could significantly reduce the OD of Kasumi-1 cells and K562 cells 450 , indicating that PSI 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 and image 3 ).

[0036] According to the growth inhibitory effect of PSI on Kasumi-1 cells, the half inhibitory concentration (IC) of PSI to Kasumi-1 cells was calculated. 50 ) is 3.84×10 -8 M.

[0037] According to the growth inhibitory effect of PSI on K562 cells, the half inhibitory concentration (IC) of P...

Embodiment 3

[0039] With different concentrations (1×10 -9 ~1×10 -6 M) PSI treatment of cell line Kasumi-1 cells containing t(8; 21) chromosomal translocation and CML cell line K562 cells containing t(9; 22) chromosomal translocation, respectively at 12, 24, 36, 48 hours after treatment Hours counted the number of living cells by fetal pan blue exclusion method and drew the growth curves of Kasumi-1 cells and K562 cells. It was found that PSI could significantly inhibit the growth of Kasumi-1 cells and K562 cells, and this effect was time-dose dependent. When the concentration of PSI is 10nM~100nM, the number of viable cells of cell line Kasumi-1 containing t(8;21) chromosomal translocation significantly decreased after PSI treatment, see Figure 4 . When the concentration of PSI is 20nM~160nM, the number of living cells of CML cell line K562 containing t(9;22) chromosome translocation significantly decreased after PSI treatment, see Figure 5 .

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Abstract

An application of the compound PSI 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 I (proteasome inhibitor I; PSI) in the preparation of medicines for treating leukemia, in particular to the application of PSI in the preparation and treatment of M2 type acute myeloid leukemia (AML M2) with t(8; 21) chromosomal translocation and Application in the medicine of 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. According to the different cell series, acute patients are divided into acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (acute myeloid leukemia, AML), and the latter is divided into several subtypes M0-M7; Leukemia (chronic myeloidleukemia, CML) and chronic lymphocytic leukemia. [0003] M2 acute myeloid leukemia (AML M2) has a high incidence, accounting for 25% of all AML, and 40%-80% of them have t(8;21) chrom...

Claims

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Application Information

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IPC IPC(8): A61K38/07A61K38/21A61K38/19A61P35/02A61K31/704
Inventor 周光飚刘大鹏胡政
Owner GUANGZHOU INST OF BIOMEDICINE & HEALTH CHINESE ACAD OF SCI
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