Application of GGPP combined and allosteric activated human FBP1 in preparation of medicine for resisting hepatocellular carcinoma

A hepatocellular carcinoma, human-derived technology, applied in the biological field to achieve the effect of inhibiting migration

Inactive Publication Date: 2021-11-26
NANJING UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] At present, there is a lack of application of geranylgeranyl pyrophosphate GGPP to bind and allosterically activate human FBP1 in the preparation of anti-hepatocellular carcinoma drugs

Method used

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  • Application of GGPP combined and allosteric activated human FBP1 in preparation of medicine for resisting hepatocellular carcinoma
  • Application of GGPP combined and allosteric activated human FBP1 in preparation of medicine for resisting hepatocellular carcinoma
  • Application of GGPP combined and allosteric activated human FBP1 in preparation of medicine for resisting hepatocellular carcinoma

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Embodiment 1

[0046] The GGPP probe with Biotin tag was used to enrich the GGPP-binding protein in primary mouse liver parenchymal cells by using the biotin-streptavidin affinity purification system and detected by mass spectrometry, and screened out multiple glycolipids Metabolism-related GGPP potential target proteins, such as fructose-1,6-bisphosphatase 1 (Fructose-1,6-bisphosphatase, FBP1) in the gluconeogenesis pathway, liver pyruvate kinase (Liver pyruvate kinase) in the glycolysis pathway , LPK) and carnitine palmitoyl transferase 1 (Carnitine palmitoyl transferase 1, CPT1) involved in lipid oxidation, etc. Among them, FBP1 due to the significance of binding to GGPP (such as Figure 5-8 shown), its important role in the regulation of glucose and lipid metabolism, and its correlation with various cancers have attracted attention.

[0047] 1. Establish a technical route for the enrichment and identification of metabolic small molecule GGPP direct binding proteins

[0048] 1.1 Design ...

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Abstract

The invention discloses an application of GGPP combined and allosteric activated human FBP1 in preparation of a medicine for resisting hepatocellular carcinoma. The amino acid sequence of the human FBP1 protein is as shown in SEQ ID No.1. According to the application of GGPP combined and allosteric activated human FBP1 in preparation of the medicine for resisting hepatocellular carcinoma, a direct binding protein action network of GGPP in normal liver is established, and a plurality of GGPP binding proteins participating in liver glycolipid metabolism regulation are screened and verified. The GGPP is specifically combined with the FBP1, the enzyme activity of the FBP1 is up-regulated, gluconeogenesis is promoted, and migration of parenchymal liver cells and liver cancer cells can be inhibited. The GGPP sensitizes the target protein FBP1 of the GGPP to couple glycolipid metabolism balance so as to regulate the molecular mechanism of hepatocellular carcinoma generation and development, and can be applied to treatment of hepatocellular carcinoma. GGPP is directly combined with the specificity of the target protein FBP1 to regulate and control the glycolipid metabolism balance of the liver, and a novel potential target, a novel medicine and a novel treatment method are provided for treatment of HCC.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to the application of geranylgeranyl pyrophosphate GGPP in combination with and allosterically activating human FBP1 in the preparation of anti-hepatocellular carcinoma drugs. Background technique [0002] The regulation of glucose and lipid metabolism homeostasis is the basis for maintaining the body's life activities. In my country, due to changes in lifestyle and dietary structure in recent decades, the glucose and lipid metabolism patterns of some populations have changed accordingly, and the incidence of metabolic syndrome such as obesity and diabetes has increased significantly. The liver, as the central organ of metabolism, bears the brunt of the long-term disturbance of glucose and lipid metabolism, leading to chronic liver diseases such as non-alcoholic fatty liver disease (NAFLD) and liver fibrosis (Liver fibrosis). Recent research results have shown that, in addition to vira...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/663A61P35/00
CPCA61K31/663A61P35/00
Inventor 方雷章竞子李朝军赵越
Owner NANJING UNIV
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