Application of glycine and derivative thereof to preparation of medicine for treating IDH (IsocitrateDehydrogenase) and FH (Fumarate Hydratase) gene mutation related tumors

A technology of glycine and derivatives, applied in the field of medicine, can solve problems such as IDH mutation and lack of effective drugs for tumors

Inactive Publication Date: 2016-01-20
FUDAN UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] In order to solve the problem that the tumor caused by IDH mutation and FH mutation lacks effective drugs, the present invention provides a

Method used

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  • Application of glycine and derivative thereof to preparation of medicine for treating IDH (IsocitrateDehydrogenase) and FH (Fumarate Hydratase) gene mutation related tumors
  • Application of glycine and derivative thereof to preparation of medicine for treating IDH (IsocitrateDehydrogenase) and FH (Fumarate Hydratase) gene mutation related tumors
  • Application of glycine and derivative thereof to preparation of medicine for treating IDH (IsocitrateDehydrogenase) and FH (Fumarate Hydratase) gene mutation related tumors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0016] Example 1. Effect of Glycine on Subcutaneous IDH Mutant Cell Implanted Tumors in Mice

[0017] Experimental method: 20 nude mice of Balb / c strain were subcutaneously implanted with IDH1 (R132C) mutated HT1080 cells, and randomly divided into control group and glycine group, with 10 mice in each group. The control group was given daily feed, and the glycine group replaced part of the casein in the daily feed with glycine, which accounted for 5% of the total feed mass. All mice had free access to food. After feeding for 3-4 weeks, the size change of the subcutaneous implanted tumor was observed, and at the end of the experiment, the mice were sacrificed to take out the implanted tumor and weigh it.

[0018] Experimental results: if figure 1 , figure 2 , image 3 As shown, the treatment did not affect the body weight of the mice, and the subcutaneous implanted tumors of mice fed with glycine in the feed were significantly smaller than those of mice fed with normal fee...

Embodiment 2

[0019] Example 2. FH mutant tumors have a hypersuccinylation phenotype, and glycine can reduce succinylation in FH mutant cells

[0020] Experimental method: 12 cases of tumor samples with FH mutation and 12 cases of FH wild-type tumor samples were used for immunohistochemistry with succinylated antibody, and the levels of succinylation in the two groups of samples were compared. The FH mutant cells were treated with glycine (final concentration 10mM, 100mM), and the succinylation level in the cells was detected by western blot.

[0021] Experimental results: if Figure 4 , Figure 5 As shown, FH-mutant tumor samples exhibit hypersuccinylation not found in FH wild-type, and glycine treatment can significantly reduce succinylation levels in FH-deficient cells.

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Abstract

The invention belongs to the technical field of medicines and particularly provides application of glycine and a derivative thereof to preparation of a medicine for treating IDH (IsocitrateDehydrogenase) and FH (Fumarate Hydratase) gene mutation related tumors. Aiming at solving the problem that effective medicines for treating IDH gene mutation and FH gene mutation related tumors are lacked, the invention provides an effective medicine aiming at the tumors. An experiment is carried out on a mouse which is inoculated with IDH mutated cells to form the tumors under the skin, and the growth speed of the tumors can be greatly reduced by orally taking the glycine, so that the life quality of the mouse is improved, protein high succinylation in the tumors is reduced, and normal functions of mitochondria of tumor cells are enhanced. The glycine has a remarkable growth inhibition effect on the tumors and can be used for preparing the medicine for treating the related tumors.

Description

technical field [0001] The invention belongs to the technical field of medicine, specifically relates to the use of glycine, and further relates to the application of glycine and its derivatives in the preparation of medicines for treating tumors (such as IDH gene mutation, FH gene mutation). Background technique [0002] Glycine (glycine), CAS number: 56-40-6, molecular weight: 75.07. [0003] Mutations in IDH (Isocitrate Dehydrogenase) can lead to malignant tumors such as glioma, leukemia, and cholangiocarcinoma, and mutations in FH (Fumarate Hydratase) can lead to malignant tumors such as type II papillary renal carcinoma. At present, it is believed that IDH mutations will produce 2HG (2-hydroxyglutarate), 2HG plays an important role in the process of tumorigenesis, and FH mutations are considered to cause tumors by affecting hypoxia-inducible factors. The mechanism of mutations leading to tumors is not yet fully understood, and there is a lack of effective drugs for its...

Claims

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Application Information

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IPC IPC(8): A61K31/198A61P35/00
Inventor 赵世民徐薇李丰
Owner FUDAN UNIV
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