Anti-tumor medicament based on alpha ketoglutaric acid and derivatives thereof

Abstract

The invention belongs to the technical field of biomedicine and relates to an anti-tumor medicament based on alpha ketoglutaric acid and derivatives thereof. The derivatives comprise various ester derivatives, amide derivatives and ether derivatives; and the alpha ketoglutaric acid comprises chemical analogues and derivatives thereof. The results of in-vitro experiments indicate that the mutation of isocitrate dehydrogenase in gliomas results in the loss of enzyme activities, the alpha ketoglutaric acid capable of growing in cells is obvious reduced, the levels of anaerobic inductor factors capable of inducing tumors and promoting the growth of the tumors are obviously improved, and the phenomenon can be reversed by exogenously replenishing absorbable alpha ketoglutaric acid. Therefore, an absorbable alpha ketoglutaric acid compound can be used for treating the gliomas, pancreatic cancers, breast cancers, liver cancers, lung cancers, gastric cancers, colorectal cancers, colon cancer and melanomas.

Description

technical field [0001] The invention belongs to the technical field of biomedicine and relates to an antitumor drug based on α-ketoglutaric acid and its derivatives. Background technique [0002] Tumor is a major disease that seriously threatens human health, characterized by unregulated rapid cell proliferation. There are many factors that lead to tumorigenesis, among which mutations in enzymes related to energy metabolism, especially some tricarboxylic acid cycle (tricarboxylic acid (TCA) cycle) enzymes, can lead to tumorigenesis. Studies have reported that mutations in the human tricarboxylic acid cycle enzyme succinatedehydrogenase (SDH) lead to phaeochromocytoma and paraganglioma (Baysal et al., 2000; Eng et al., 2003). Then another study reported that fumarate dehydrogenase (fumarate hydratase (FH )) Mutation or downregulation of expression can lead to the occurrence of gastric and colorectal carcinoma (Frederiksen et al., 2003; Habano et al., 2003). [0003] In 2003...

AI Technical Summary

Problems solved by technology

[0003] In 2003, some studies put forward the hypothesis that the mutation or expression downregulation of SDH and FH leads to the downregulation of metabolism, especially the tricarboxylic acid cycle, resulting in the production of a large number of oxygen free radicals

[0006] Recent studies of isocitrate dehydrogenase 1 and isocitrate dehydrogenase 2 mutations in glioma have shown that mutations in one or both of these genes can lead to isocitrate dehydrogenase 1 and isocitrate dehydrogenase 2 mutations. The dominant negative inhibition of isocitrate dehydrogenase 2 leads to a significant decrease in the activity of isocitrate dehydrogenase in cells, thereby reducing the concentration of α-ketoglutarate in cells and promoting the increase of HIF1a (zhao et al, 2009)

Images