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Clinical Application of Glutamine Powder Enzyme Inhibitors
- Aug 09, 2019 -

The dependence of cancer cells on glutamine powder metabolism makes them a potential target for anti-cancer. Many compounds for glutamine metabolism, from initial transport to subsequent conversion to alpha-ketoglutarate, have become a research hotspot.


Although most of them are still in the pre-clinical "tool synthesis" stage or limited by the toxicity of compounds, glutaminase (GLS) mutant inhibitors have shown great potential in the model of preclinical cancer. A very active compound, CB-839, has entered clinical trials.


There are two main types of glutaminase in human body: kidney-type glutaminase (GLS) and liver-type glutaminase (GLS2).

Tumor cells overactivate renal glutaminase (GLS). GLS2 mainly acts on non-cancer cells and catalyzes glutamine metabolism.

The multipotency of glutamine powder in cell function, such as energy synthesis, macromolecule synthesis, mTOR activation and reactive oxygen species balance, makes GLS inhibitors play a synergistic role in combination therapy.

Inhibition of glutaminase gene can prevent epithelial cells from transforming into mesenchymal cells. This step is the key step for the invasion and final metastasis of cancer cells. Therefore, prevention of metastasis may be an important role of GLS inhibitors in combination therapy of glutamine powder metabolic inhibition.

Tumor immunization has also become the most promising treatment to date, such as blocking immune checkpoint PD-1 monoclonal antibodies or using engineered chimeric antigen receptor (CAR) T cells.

These methods require immune cells to play a role in the tumor microenvironment, and metabolic inhibitors in vivo may also widely affect the immune function. Recent studies have shown that immune cells compete with cancer cells for glucose, and glutamine powder may be a similar mechanism.

In fact, glutamine metabolism plays an important role in activating T cells and regulating the transformation of CD4 + T cells to inflammatory subtypes.

Glutamine powder is critical to the activation of T cells by cancer tinea. By blocking the glutamine powder pathway in cancer cells, the content of amino acids in tumor microenvironment can be increased, and the killing effect of immune cells can be enhanced.

The combination of GLS inhibitor CB-839 and cancer immunity has entered the first and second clinical stage.


Tumor microenvironment metabolites and tumor immunity have also become the fragrant baboons in the field of tumor metabolism. Recently, hot IDO inhibitors are the representative of them.

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