Application of compound PS-341 in preparation of medicine for treating acute pulp leucocythemia

A technology of PS-341 and acute myeloid leukemia, which is applied in the application field of compound PS-341 in the preparation of drugs for the treatment of acute myeloid leukemia, which can solve the problem of median survival time of less than 2 years, survival rate of less than 40%, treatment failure, etc. problems, to achieve the effects of easy changes in blood drug concentration, significant curative effect, and convenient medication

Inactive Publication Date: 2008-12-10
GUANGZHOU INST OF BIOMEDICINE & HEALTH CHINESE ACAD OF SCI
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  • Abstract
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  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The treatment of AMLM2 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%.
In view of the different causes of different tumors, proteasome also has different components or subunits, proteasome inhibitors have different effects on different subunits in different tumors, and PS-341 has different effects on myeloid leukemia, especially with t(8 ;21) There is no report on whether the M2 acute myeloid leukemia with chromosomal translocation has therapeutic effect, the principle of treatment and the concentration of effective treatment.

Method used

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  • Application of compound PS-341 in preparation of medicine for treating acute pulp leucocythemia
  • Application of compound PS-341 in preparation of medicine for treating acute pulp leucocythemia
  • Application of compound PS-341 in preparation of medicine for treating acute pulp leucocythemia

Examples

Experimental program
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Effect test

Embodiment 1

[0024] U937 cells transfected with AML1-ETO fusion gene (U937-A / E cells) were treated with different concentrations of PS-341, and after 24 hours of treatment, the cells were collected and lysed with 1× cell lysate to extract protein, and then treated with anti-ETO antibody ( (purchased from Santa Cruz, USA) for Western blot immunoblotting experiments. It was found that PS-341 could regulate the expression of AML1-ETO fusion protein, partially degrade the AML1-ETO protein and produce degradation bands, see figure 1 , where the left is the control, and the right is the change of AML1-ETO fusion protein after 24 hours of treatment with PS-341 at a concentration of 10 nM.

Embodiment 2

[0026] With different concentrations of compound PS-341 (1×10 -10 ~1×10 -6 M) Treat Kasumi-1 cells, add 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfonic acid) after 44 hours Acid phenyl)-2H-tetrazolium monosodium salt (WST-8) CCK-8 detection reagent, and then incubated for 4 hours, then measured its absorbance at 450nm (OD 450 ). It was found that PS-341 treatment could significantly reduce the OD of Kasumi-1 cells 450 , PS-341 can significantly inhibit the proliferation of Kasumi-1 cells, and the inhibition rate is positively correlated with the drug concentration (see figure 2 ). According to the growth inhibitory effect of PS-341 on Kasumi-1 cells, calculate the half maximal inhibitory concentration (IC) of PS-341 on Kasumi-1 cells 50 ) is 5.2×10 -9 M.

Embodiment 3

[0028]Kasumi-1 cells were treated with different concentrations of PS-341 (0.1nM~5nM)PS-341, and the number of viable cells was counted by placepan blue exclusion method at 12, 24, and 48 hours after treatment, and the number of Kasumi-1 cells was plotted. According to the growth curve, it was found that PS-341 could significantly inhibit the growth of Kasumi-1 cells, and this effect was time-dose dependent. When the concentration of PS-341 was 1-5nM, the number of living cells of Kasumi-1 treated with PS-341 was significantly reduced, as shown in image 3 shown.

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Abstract

The present invention relates to the application of compound PS-341 in preparing medicine for treating M2 type acute myeloid leukemia with t(8;21) chromosomal translocation, and its effective concentration is 1×10-9~1×10-7M. The compound PS-341 provides a new therapeutic drug for patients with M2 acute myeloid leukemia. It has the advantages of small dose, moderate cost, convenient medication and small side effects, and can be used to prepare and treat M2 acute myeloid leukemia in the initial and relapsed stages. Drugs for myeloid leukemia patients.

Description

technical field [0001] The present invention relates to the application of compound PS-341 in the preparation of medicines for treating acute myeloid leukemia, especially in the preparation of medicines for treating M2 type acute myeloid leukemia (AML M2) with t(8;21) chromosomal translocation application. Background technique [0002] Leukemia is a group of hematopoietic stem / progenitor cell diseases with abnormal genome, which can be divided into acute and chronic. The acute ones are divided into acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), and the latter is divided into M0~M7. Subtype. [0003] The incidence of AML M2 is higher, accounting for 25% of all AML, of which 40%-80% have t (8; 21) chromosome translocation. This translocation produces an AML1-ETO fusion gene, and the encoded AML1-ETO fusion protein not only competes with wild-type AML1 for the AML1-binding site TG(T / C)GGT on the target gene, but also actively represses the transcription ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K38/55A61P35/02A61K31/704A61K38/19
Inventor 周光飚谢军陈竺刘大鹏
Owner GUANGZHOU INST OF BIOMEDICINE & HEALTH CHINESE ACAD OF SCI
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