Application of isoalantolactone in preparation of medicines for resisting chronic myeloid leukemia

A kind of technology of isogeolactone and chronic granulocytes, which is applied in the direction of antineoplastic drugs, drug combinations, pharmaceutical formulas, etc., can solve the problems of non-removal, drug resistance ratio, and low complete remission rate, and achieve the effect of easy acquisition

Inactive Publication Date: 2015-07-01
上海交通大学医学院附属第三人民医院
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Problems solved by technology

With the affirmation of the clinical efficacy of Imatinib, its defects are gradually discovered: Imatinib is mainly aimed at patients with early CML, and the complete remission rate of Imatinib for patients in the middle and late stages is less than 30%; some patients may develop Imatinib resistance and the proportion is increasing year by year. Associated with BCR-ABL mutation or gene amplification overexpression leading to reduced sensitivity to Imatinib
In response to these problems,...

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  • Application of isoalantolactone in preparation of medicines for resisting chronic myeloid leukemia
  • Application of isoalantolactone in preparation of medicines for resisting chronic myeloid leukemia
  • Application of isoalantolactone in preparation of medicines for resisting chronic myeloid leukemia

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[0026] In the following, the present invention will be described in detail and specifically through specific examples, so as to better understand the present invention, but the following examples do not limit the scope of the present invention.

[0027] In order to screen natural small molecule compounds that can degrade Bcr-Abl protein, we first established a cell screening model that can reflect protein stability: GFP-fused BCR-ABL was stably transfected into K562 cells, and the green fluorescent To change, screen for small molecules that can reduce Bcr-Abl protein levels. Through the screening of a series of natural products, we found a natural small molecule compound - Isoalantolactone (IsoA), which can significantly reduce the GFP-Bcr-Abl green fluorescence signal ( figure 1 ). Heterocarcinolide is isolated from the root of the plant Inula inulae in the genus Asteraceae, and belongs to the eucalyptane-type sesquiterpene lactone compound ( figure 1 ), is the main active ...

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Abstract

The invention provides application of isoalantolactone in preparation of medicines for resisting chronic myeloid leukemia by screening cell lines with built GFP-Bcr-Abl. The inventor finds out that the anti-CML activity of the isoalantolactone is realized by specifically inducing autolysosome in a K562 cell to actively degrade Bcr-Abl fusion protein, and simultaneously finds out that the isoalantolactone is capable of significantly inhibiting formation of Bcr-Abl positive stem cell cloning in newly diagnosed chronic myeloid patients and medicine-resistant patients. The possibility is provided for treatment medicine-resistant or recurrent CML patients by inducing degradation of the Bcr-Abl fusion protein through a natural small molecular compound of the isoalantolactone.

Description

technical field [0001] The present invention relates to the application of a natural small molecule compound isogastrolide in the preparation of anti-chronic myelogenous leukemia medicine. Background technique [0002] Leukemia is a kind of malignant clonal disease with abnormal hematopoietic stem cells. In my country, the incidence of leukemia is increasing year by year, accounting for about 5% of the total cancer incidence. Among them, chronic myelogenous leukemia (CML) accounts for 20% of adult leukemia. More than 90% of CML patients can detect a specific Philadelphia chromosome (Philadelphia, Ph), that is, t(9;22)(q34;q11) chromosome translocation, and the C-Abl gene of the long arm of chromosome 9 is translocated to The long arm breakpoint concentration region (BCR) on chromosome 22 produces the oncogenic BCR-ABL fusion gene, which is detected in 95% of patients with chronic myelogenous leukemia. The Bcr-Abl fusion protein encoded by the fusion gene (Bcr-Abl fusion p...

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Application Information

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IPC IPC(8): A61K31/365A61P35/02A61P35/00
Inventor 高丰厚吴英理韦炜张超卢静刘珍
Owner 上海交通大学医学院附属第三人民医院
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