17h ago in General
What can inhibit Glutamine?
FROM CHAT GPT:
Glutamine inhibition is often targeted in cancer therapy or metabolic research to restrict glutamine's role in cellular processes, especially since many tumors are glutamine-dependent. Here are some common approaches and compounds used for glutamine inhibition:
1. Glutaminase (GLS) Inhibitors:
Glutaminase is an enzyme that converts glutamine into glutamate, a key step in glutamine metabolism. Inhibiting glutaminase can reduce glutamine availability for cell growth, especially in cancer cells.
- CB-839 (Telaglenastat): One of the most well-known glutaminase inhibitors used in clinical trials for cancer therapy.
- BPTES: An early inhibitor of GLS, although less potent than CB-839.
2. Glutamine Analogues:
These are structural analogs of glutamine that can compete with glutamine for uptake and utilization in cells.
- DON (6-Diazo-5-oxo-L-norleucine): A classic glutamine analog that inhibits multiple enzymes involved in glutamine metabolism.
- Azaserine: Another glutamine analog that inhibits enzymes utilizing glutamine, particularly in nucleotide synthesis.
3. ASCT2 (SLC1A5) Inhibitors:
ASCT2 is a glutamine transporter that facilitates the uptake of glutamine into cells. Blocking this transporter can limit glutamine's availability inside the cell.
- V-9302: A small-molecule inhibitor targeting ASCT2, reducing glutamine uptake.
4. mTOR Inhibitors:
Since glutamine can activate the mTOR pathway, which is crucial for cell growth and proliferation, mTOR inhibitors can indirectly affect glutamine metabolism.
- Rapamycin (Sirolimus): An mTOR inhibitor that can be used to suppress the glutamine-driven mTOR signaling cascade.
5. GLUD (Glutamate Dehydrogenase) Inhibitors:
GLUD converts glutamate (derived from glutamine) into α-ketoglutarate for use in the tricarboxylic acid (TCA) cycle. Inhibiting GLUD can reduce the energy and biosynthetic precursors provided by glutamine metabolism.
6. Inhibition of Amino Acid Synthesis Pathways:
Many tumors use glutamine for nucleotide and amino acid synthesis. Inhibiting enzymes in these pathways can indirectly affect glutamine metabolism:
- Methotrexate: Inhibits dihydrofolate reductase, affecting glutamine's role in purine and pyrimidine synthesis.
These strategies are particularly useful in cancer research, where cells often rely on glutamine for energy, redox balance, and biosynthesis. Targeting glutamine metabolism is emerging as a therapeutic approach to disrupt cancer cell growth.
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What can inhibit Glutamine?
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