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Application of ATM inhibitor to preparation of medicine for restraining recurring of acute lymphoblastic leukemia

A technology of acute lymphocytes and inhibitors, applied in the application field of ATM inhibitors in the preparation of drugs for inhibiting the recurrence of acute lymphoblastic leukemia, which can solve the problems of relapse and cure rate of less than 40% in children, and reduce the relapse rate , the effect of increasing sensitivity

Inactive Publication Date: 2018-12-21
SHANGHAI CHILDRENS MEDICAL CENT AFFILIATED TO SHANGHAI JIAOTONG UNIV SCHOOL OF MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The treatment and prognosis of children with ALL have been significantly improved, but 15% to 20% of children will relapse, and the cure rate after relapse is less than 40%

Method used

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Examples

Experimental program
Comparison scheme
Effect test

specific Embodiment approach 1

[0008] Embodiment 1: In this embodiment, ATM inhibitors are used as the active ingredient in the preparation of drugs for inhibiting the recurrence of acute lymphoblastic leukemia; especially the active ingredient in the preparation of drugs for inhibiting the recurrence of childhood acute lymphoblastic leukemia after chemotherapy.

specific Embodiment approach 2

[0009] Specific embodiment two: In this embodiment, ATM inhibitors are used as active ingredients in the preparation of drugs for inhibiting the recurrence of acute lymphoblastic leukemia; the ATM inhibitors are inhibitor Ku60019, inhibitor KU-55933, inhibitor CP-466722, inhibitor agent AZD6738 or inhibitor ETP46464.

[0010] In this embodiment, the ATM inhibitors Ku60019, KU-55933, CP-466722, AZD6738, and ETP46464 were all purchased from MCE Company.

Embodiment 1

[0012] 1. Up-regulated expression of cytokines in acute lymphocytes after chemotherapy

[0013] Two acute lymphoblastic leukemia cell lines (Nalm-6 and Reh) were treated with different chemotherapeutic drugs (Ara-C, 6MP, MTX, VCR, DNR, CTX and DXMS), and the cytokines ( CCL3, CCL4 and GDF-15) expression levels, it was found that except for DXMS, the rest of the drugs could significantly increase the mRNA levels of CCL3, CCL4 and GDF-15 in cells.

[0014] 2. Confirm that cytokine upregulation is accomplished through ATM-mediated DDR signaling pathway

[0015] The mechanism of action of cytarabine (Ara-C) and purine (6-MP and 6-TG), commonly used in clinical practice, is mainly to inhibit the DNA synthesis pathway, induce the DNA damage response (DDR) in cells, and then lead to the death of tumor cells. In this example, different concentrations of Ara-C were used to treat ALL cell lines (Nalm-6 and Reh), and the total protein was extracted to detect the expression of some prote...

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Abstract

The invention relates to application of an ATM inhibitor to preparation of a medicine for restraining recurring of acute lymphoblastic leukemia(ALL), and relates to application of a molecule adjustingand controlling agent to preparation of the medicine for restraining recurring of acute lymphoblastic leukemia. The ATM inhibitor is used as active components for preparing the medicine for restraining recurring of acute lymphoblastic leukemia. According to a molecule mechanism being tolerant to drugs and recurring after treatment of the acute lymphoblastic leukemia, a treatment medicine with a fully-new system is established, targeted medicine application can be realized, and the medicine has great importance in reduction of the recurring rate of child patients suffering from the acute lymphoblastic leukemia after chemotherapy.

Description

technical field [0001] The invention relates to the application of a molecular regulator in the preparation of medicines for inhibiting the recurrence of acute lymphocytic leukemia. Background technique [0002] Acute lymphoblastic leukemia (ALL) is a major disease that seriously endangers human health, and is the most common tumor in children and adolescents. The treatment and prognosis of children with ALL have improved significantly, but 15% to 20% of children will relapse, and the cure rate after relapse is less than 40%. Contents of the invention [0003] Aiming at the problems of high relapse rate and low cure rate of relapsed children after chemotherapy for children with ALL, the invention provides an application of an ATM inhibitor in the preparation of a drug for inhibiting relapse of acute lymphocytic leukemia. [0004] The invention uses the ATM inhibitor as the active ingredient in the preparation of the medicine for inhibiting the recurrence of acute lymphocy...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/5377A61K31/538A61K31/517A61P35/02
CPCA61K31/517A61K31/5377A61K31/538A61P35/02
Inventor 段才闻陈亚莉张梦怡唐超周斌兵
Owner SHANGHAI CHILDRENS MEDICAL CENT AFFILIATED TO SHANGHAI JIAOTONG UNIV SCHOOL OF MEDICINE
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