OGT inhibitor and application thereof

A technology of inhibitors and kits, applied in the field of biomedicine, can solve problems such as easy tumor recurrence, cognitive dysfunction, and low survival rate

Inactive Publication Date: 2021-09-10
ACADEMY OF MILITARY MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the special location of myeloblastoma and the young age of the patient, the operation is very difficult, and it is difficult to completely remove the tumor. As a result, the tumor is prone to recurrence after surgery, and the prognosis of the patient is poor, which seriously affects the health of the patient. survival rate is still low
Therefore, in addition to surgical resection, combined therapy often supplemented with postoperative radiotherapy can significantly improve the patient's survival rate and reduce the postoperative recurrence rate, but it may be accompanied by long-term toxic and side effects of the central nervous system of the patient. , such as hearing loss, cognitive impairment, neurological and mental retardation, etc.

Method used

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  • OGT inhibitor and application thereof
  • OGT inhibitor and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] Example 1 OSMI-1 inhibits the generation of SHH subtype medulloblastoma

[0054] 1. Experimental materials

[0055] Mouse: Atoh1-Cre; SmoM2

[0056] Reagent: OSMI-1 (Sigma, SmL1621)

[0057] 2. Experimental steps

[0058] Experimental procedure: Atoh1-Cre; SmoM2 SHH medulloblastoma tumor mice born 14 days after birth were randomly selected and administered with OSMI-1 and the corresponding volume of solvent DMSO for three days and one day off. The survival curves of the two groups of mice were counted, and the weights of the cerebellum of the two groups of mice at P30 were measured for comparison.

[0059] Specific experimental operation:

[0060] 1. Mouse hybridization: first choose OGT F / F Hybridize with Atoh1-Cre to obtain Atoh1-Cre; OGT F / -Heterozygous, cross SmoM2 and Atoh1-Cre at the same time to obtain Atoh1-Cre; SmoM2 heterozygous, and then further cross these two heterozygous mice to obtain Atoh1-Cre; OGT F / - ;SmoM2 F / - , by adding Atoh1-Cre; OGT F / - ...

Embodiment 2

[0067] Example 2 OSMI-1 inhibits the proliferation of human SHH subtype medulloblastoma DaoY cells

[0068] 1. Experimental materials

[0069] Cell: DaoY (ATCC)

[0070] Reagents: OSMI (Sigma, Sml1621), Thiamet-G (Sigma, Sml0244), Ki67 (BD, 550609), EdU detection kit (Ribo), Giemsa stain (Prilite), cck8 stain (North Weizan) 2. Experimental steps

[0071] Experimental procedure: The cultured DaoY cells were treated with DMSO, OSMI-1 and Thiamet-G, the cell proliferation marker Ki-67 immunofluorescence detection and EdU infiltration experiment were performed on these five groups of cells, and the single-cell colonies were also performed at the same time. Staining and cck8 cell proliferation detection experiments.

[0072] Specific experimental operation:

[0073] 1. Differently treated DaoY cell proliferation markerEdU and Ki67 labeling: EdU staining was done according to the Protocol of the EdU labeling kit. First, each group of DaoY cells was planted in a confocal dish, a...

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PUM

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Abstract

The invention relates to an OGT inhibitor and application thereof. The invention provides an application of an OGT inhibitor in prevention or treatment of myeloblastoma or inhibition of cell proliferation of myeloblastoma. In a specific embodiment, the OGT inhibitor can inhibit the generation and cell proliferation of the medulloblastoma, which indicates that the OGT inhibitor has good medicinal potential in the aspect of preventing or treating the medulloblastoma. The invention also provides a method for screening candidate drugs for preventing or treating myeloblastoma or inhibiting cell proliferation of myeloblastoma.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to an OGT inhibitor and its application. Background technique [0002] Medulloblastoma (MB) is a malignant tumor of the posterior cranial fossa, often originating from the vermis of the cerebellum or the posterior medullary velum. The tumor cells grow very rapidly and have a high ability to invade and migrate, and it is very easy to circulate through the cerebrospinal fluid. Spread throughout the central nervous system. MB is the most common intracranial malignancy in children, accounting for 20% of central nervous system tumors in children, and double the proportion of cerebellar tumors in children, up to 40%. The incidence rate of European and American whites is higher than that of Asians. There are more men than women in the affected population. The peak age is 8 years old, and most of them occur before 20 years old. [0003] In 2007, the World Health Organization (WHO) d...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K31/4709C07D409/14A61P35/00C12Q1/48
CPCA61K45/06A61K31/4709C07D409/14A61P35/00C12Q1/48
Inventor 吴海涛陈丽萍李莹
Owner ACADEMY OF MILITARY MEDICAL SCI
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