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

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...

AI Technical Summary

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, continue to develop a new generation of tyrosine kinase inhibitors targeting Bcr-Abl fusion proteins along the existing ideas, such as the development and marketing of new generation inhibitors of Nilotinib, Dasatinib and Ponatinib, which is certainly a solution to the problem An option, but given previous experience, this option does not cure CML at its root

Because in this strategy, only the tyrosine kinase activity of Bcr-Abl is selectively inhibited, but the Bcr-Abl protein is not removed

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